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1. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author

Francine Garnache-Ottou, Chrystelle Vidal, Sabeha Biichlé, Florian Renosi, Eve Poret, Maïder Pagadoy, Maxime Desmarets, Anne Roggy, Estelle Seilles, Lou Soret, Françoise Schillinger, Sandrine Puyraimond, Tony Petrella, Claude Preudhomme, Christophe Roumier, Elisabeth A. MacIntyre, Véronique Harrivel, Yohan Desbrosses, Bérengère Gruson, Franck Geneviève, Sylvain Thepot, Yuriy Drebit, Thibaut Leguay, François-Xavier Gros, Nicolas Lechevalier, Pascale Saussoy, Véronique Salaun, Edouard Cornet, Zehaira Benseddik, Richard Veyrat-Masson, Orianne Wagner-Ballon, Célia Salanoubat, Marc Maynadié, Julien Guy, Denis Caillot, Marie-Christine Jacob, Jean-Yves Cahn, Rémy Gressin, Johann Rose, Bruno Quesnel, Estelle Guerin, Franck Trimoreau, Jean Feuillard, Marie-Pierre Gourin, Adriana Plesa, Lucile Baseggio, Isabelle Arnoux, Norbert Vey, Didier Blaise, Romaric Lacroix, Christine Arnoulet, Blandine Benet, Véronique Dorvaux, Caroline Bret, Bernard Drenou, Agathe Debliquis, Véronique Latger-Cannard, Caroline Bonmati, Marie-Christine Bene, Pierre Peterlin, Michel Ticchioni, Pierre-Simon Rohrlich, Anne Arnaud, Stefan Wickenhauser, Valérie Bardet, Sabine Brechignac, Benjamin Papoular, Victoria Raggueneau, Jacques Vargaftig, Rémi Letestu, Daniel Lusina, Thorsten Braun, Vincent Foissaud, Jérôme Tamburini, Hind Bennani, Nicolas Freynet, Catherine Cordonnier, Magali Le Garff-Tavernier, Nathalie Jacques, Karim Maloum, Damien Roos-Weil, Didier Bouscary, Vahid Asnafi, Ludovic Lhermitte, Felipe Suarez, Etienne Lengline, Frédéric Féger, Giorgia Battipaglia, Mohamad Mohty, Sabrina Bouyer, Ouda Ghoual, Elodie Dindinaud, Caroline Basle, Mathieu Puyade, Carinne Lafon, Thierry Fest, Mikael Roussel, Xavier Cahu, Elsa Bera, Sylvie Daliphard, Fabrice Jardin, Lydia Campos, Françoise Solly, Denis Guyotat, Anne-Cécile Galoisy, Alice Eischen, Caroline Mayeur-Rousse, Blandine Guffroy, Christian Recher, Marie Loosveld, Alice Garnier, Vincent Barlogis, Maria Alessandra Rosenthal, Sophie Brun, Nathalie Contentin, Sébastien Maury, Mary Callanan, Christine Lefebvre, Natacha Maillard, Patricia Okamba, Christophe Ferrand, Olivier Adotevi, Philippe Saas, Fanny Angelot-Delettre, Delphine Binda, and Eric Deconinck

Subjects
Specialties of internal medicine, RC581-951
Abstract

Abstract: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Published
2019
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2. Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape

Author

Loria Zalmaï, Pierre-Julien Viailly, Sabeha Biichle, Meyling Cheok, Lou Soret, Fanny Angelot-Delettre, Tony Petrella, Marie-Agnès Collonge-Rame, Estelle Seilles, Sandrine Geffroy, Eric Deconinck, Etienne Daguindau, Sabrina Bouyer, Elodie Dindinaud, Victor Baunin, Magali Le Garff-Tavernier, Damien Roos-Weil, Orianne Wagner-Ballon, Véronique Salaun, Jean Feuillard, Sophie Brun, Bernard Drenou, Caroline Mayeur-Rousse, Patricia Okamba, Véronique Dorvaux, Michel Tichionni, Johann Rose, Marie Thérèse Rubio, Marie Christine Jacob, Victoria Raggueneau, Claude Preudhomme, Philippe Saas, Christophe Ferrand, Olivier Adotevi, Christophe Roumier, Fabrice Jardin, Francine Garnache-Ottou, and Florian Renosi

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Neoplasms involving plasmacytoid dendritic cells (pDC) include blastic pDC neoplasms (BPDCN) and other pDC proliferations, where pDC are associated with myeloid malignancies: most frequently chronic myelomonocytic leukemia (CMML) but also acute myeloid leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDC in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DC (cDC) associated in the same sample, by phenotypic and molecular analyses (targeted next-generation sequencing, 70 genes). We compared 15 pDCAML at diagnosis with 21 BPDCN and 11 normal pDC from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDC (4-36%), monocytes in 14 cases (1-10%) and cDC (two cases, 4.8-19%). pDC in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56– in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a prepDC stage. In all cases, pDC, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite the low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.

Published
2020
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4. Transcriptomic and genomic heterogeneity in blastic plasmacytoid dendritic cell neoplasms: from ontogeny to oncogenesis

Author

Christophe Ferrand, Philippe Saas, Etienne Daguindau, Anne Roggy, Sandrine Geffroy, Sabrina Bouyer, Pierre-Julien Viailly, Olivier Adotevi, Mary Callanan, Sabeha Biichle, Elizabeth Macintyre, Francine Garnache-Ottou, Tony Petrella, Jacques Colinge, Christophe Roumier, Florian Renosi, Véronique Harrivel, Véronique Salaun, Pascale Saussoy, Eric Deconinck, Ambre Giguelay, Fanny Angelot-Delettre, Jean Feuillard, Vahid Asnafi, Claude Preudhomme, Fabrice Jardin, Meyling Cheok, Pascal Fuseau, Lou Soret, UCL - (SLuc) Service de biologie hématologique, and UCL - SSS/IREC/SLUC - Pôle St.-Luc

Subjects
Myeloid, Carcinogenesis, Plasmacytoid dendritic cell, Biology, medicine.disease_cause, SOXC Transcription Factors, Immunophenotyping, CDKN2A, medicine, Humans, Lectins, C-Type, Receptors, Immunologic, Acute leukemia, Myeloid Neoplasia, Membrane Glycoproteins, Myeloproliferative Disorders, Dendritic Cells, Genomics, Hematology, ETV6, medicine.anatomical_structure, Cancer research, Transcriptome, SNP array
Abstract

Oncogenesis and ontogeny of blastic plasmacytoid dendritic cell neoplasm (BPDCN) remain uncertain, between canonical plasmacytoid dendritic cells (pDCs) and AXL+ SIGLEC6+ DCs (AS-DCs). We compared 12 BPDCN to 164 acute leukemia by Affymetrix HG-U133 Plus 2.0 arrays: BPDCN were closer to B-cell acute lymphoblastic leukemia (ALL), with enrichment in pDC, B-cell signatures, vesicular transport, deubiquitination pathways, and AS-DC signatures, but only in some cases. Importantly, 1 T-cell ALL clustered with BPDCN, with compatible morphology, immunophenotype (cCD3+ sCD3− CD123+ cTCL1+ CD304+), and genetics. Many oncogenetic pathways are deregulated in BPDCN compared with normal pDC, such as cell-cycle kinases, and importantly, the transcription factor SOX4, involved in B ontogeny, pDC ontogeny, and cancer cell invasion. High-throughput sequencing (HaloPlex) showed myeloid mutations (TET2, 62%; ASXL1, 46%; ZRSR2, 31%) associated with lymphoid mutations (IKZF1), whereas single-nucleotide polymorphism (SNP) array (Affymetrix SNP array 6.0) revealed frequent losses (mean: 9 per patient) involving key hematological oncogenes (RB1, IKZF1/2/3, ETV6, NR3C1, CDKN2A/B, TP53) and immune response genes (IFNGR, TGFB, CLEC4C, IFNA cluster). Various markers suggest an AS-DC origin, but not in all patients, and some of these abnormalities are related to the leukemogenesis process, such as the 9p deletion, leading to decreased expression of genes encoding type I interferons. In addition, the AS-DC profile is only found in a subgroup of patients. Overall, the cellular ontogenic origin of BPDCN remains to be characterized, and these results highlight the heterogeneity of BPDCN, with a risk of a diagnostic trap.

Published
2021
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5. Variant form of hairy cell leukemia

Author

Edouard Cornet, Véronique Salaun, Margaux Wiber, Elsa Maitre, Dina Naguib, Xavier Troussard, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie, Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
medicine.medical_treatment, Splenectomy, lcsh:Medicine, Case Report, Case Reports, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, BRAFV600E, 0302 clinical medicine, medicine, hairy cell leukemia, Hairy cell leukemia, In patient, KDM6A, Hairy Cell Leukemia Variant, lcsh:R5-920, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, BRAF V600E, Ibrutinib, lcsh:R, Refractory Disease, General Medicine, medicine.disease, 3. Good health, chemistry, 030220 oncology & carcinogenesis, Variant form, Cancer research, chronic B‐lymphoproliferative disorder, Hairy Cell, business, hairy cell leukemia variant, lcsh:Medicine (General), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Mature lymphoid B-cell proliferations with hairy cells represent heterogeneous entities where specific diagnosis is difficult but important since it impacts therapeutic management. The clinical cases of variant hairy cell leukemia reported herein illustrate the persistence of a clear interest in the use of splenectomy as a therapeutic alternative. Furthermore, ibrutinib appears to be a promising treatment in patients with relapsed/refractory disease.

Published
2019
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6. [Composite lymphoma: Case report of a coexisting follicular and mantle cell lymphoma in situ in a cervical node]

Author

Camille, Linard, Audrey, Lasne-Cardon, Véronique, Salaun, Pierre, Rousselot, and Marine, Dorbeau

Subjects
Adult, Aged, 80 and over, Male, Composite Lymphoma, Humans, Lymphoma, Mantle-Cell, Lymphoma, Follicular
Abstract

Composite lymphoma represents 1-4% of lymphomas. Only 8 case reports concerned coexisting follicular lymphoma and mantle cell lymphoma. Here, we report the case of an 81 years old man who has been diagnosed with a composite follicular and in situ mantle cell lymphoma. The use of a large panel of immunohistochemical stains associated with the flow cytometry results have allowed us to make this particular diagnosis. We highlight here a common clonal origin of the composite lymphoma's two entities, as described in previous publications.

Published
2021

7. Linking the KIR phenotype with STAT3 and TET2 mutations to identify chronic lymphoproliferative disorders of NK cells

Author

Thierry Fest, Mikael Roussel, Cedric Pastoret, Fabienne Desmots, Véronique Salaun, Anne-Violaine Doncker, Gandhi Damaj, Aline Moignet, Marie-Laure Boulland, Gaëlle Drillet, Céline Pangault, Simon Le Gallou, Alexia Thannberger, Thierry Lamy, Richard Veyrat-Masson, Olivier Tournilhac, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], CH de Saint-Malo [Broussais], Hopital Privé Sévigné [Cesson-Sévigné, France], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematology Laboratory at Rennes University Medical Center, Association pour le développement de l’Hématologie Oncologie (ADHO), Chard-Hutchinson, Xavier, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Myeloid, [SDV]Life Sciences [q-bio], Immunology, Lymphoproliferative disorders, [SDV.CAN]Life Sciences [q-bio]/Cancer, NK cells, Biology, medicine.disease_cause, Biochemistry, Transcriptome, Pathogenesis, STAT3, large granular lymphocyte leukemia, 03 medical and health sciences, 0302 clinical medicine, chronic lymphoproliferative disorders of NK cells, [SDV.CAN] Life Sciences [q-bio]/Cancer, KIR phenotype, medicine, 030304 developmental biology, 0303 health sciences, Mutation, TET2, Cell Biology, Hematology, medicine.disease, Phenotype, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], Haematopoiesis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research
Abstract

Distinguishing chronic lymphoproliferative disorders of NK cells (CLPD-NK) from reactive NK-cell expansion is challenging. We assessed the value of killer immunoglobulin-like receptor(KIR) phenotyping and targeted high-throughput sequencing in a cohort of 114 consecutive patients with NK cell proliferation, retrospectively assigned to a CLPD-NK group (n = 46) and a reactive NK group (n = 68). We then developed an NK-cell clonality score combining flow cytometry and molecular profiling with a positive predictive value of 93%. STAT3 and TET2 mutations were respectively identified in 27% and 34% of the patients with CLPD-NK, constituting a new diagnostic hallmark for this disease. TET2-mutated CLPD-NK preferentially exhibited a CD16low phenotype, more frequently displayed a lower platelet count, and was associated with other hematologic malignancies such as myelodysplasia. To explore the mutational clonal hierarchy of CLPD-NK, we performed whole-exome sequencing of sorted, myeloid, T, and NK cells and found that TET2 mutations were shared by myeloid and NK cells in 3 of 4 cases. Thus, we hypothesized that TET2 alterations occur in early hematopoietic progenitors which could explain a potential link between CLPD-NK and myeloid malignancies. Finally, we analyzed the transcriptome by RNA sequencing of 7 CLPD-NK and evidenced 2 groups of patients. The first group displayed STAT3 mutations or SOCS3 methylation and overexpressed STAT3 target genes. The second group, including 2 TET2-mutated cases, significantly underexpressed genes known to be downregulated in angioimmunoblastic T-cell lymphoma. Our results provide new insights into the pathogenesis of NK-cell proliferative disorders and, potentially, new therapeutic opportunities.

Published
2021
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8. Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape

Author

Fabrice Jardin, Elodie Dindinaud, Meyling Cheok, Fanny Angelot-Delettre, Victor Baunin, Caroline Mayeur-Rousse, Victoria Raggueneau, Bernard Drenou, Christophe Ferrand, Patricia Okamba, Johann Rose, Marie-Thérèse Rubio, Etienne Daguindau, Véronique Dorvaux, Loria Zalmaï, Eric Deconinck, Florian Renosi, Claude Preudhomme, Pierre-Julien Viailly, Olivier Adotevi, Christophe Roumier, Michel Tichionni, Francine Garnache-Ottou, Damien Roos-Weil, Sabrina Bouyer, Sabeha Biichle, Sandrine Geffroy, Marie-Agnès Collonge-Rame, Marie Christine Jacob, Tony Petrella, Jean Feuillard, Philippe Saas, Magali Le Garff-Tavernier, Lou Soret, Véronique Salaun, Orianne Wagner-Ballon, Estelle Seilles, Sophie Brun, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Université de Montréal (UdeM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CH La Rochelle, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Henri Mondor, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Limoges, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Strasbourg, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Le Mans (CH Le Mans), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier de Versailles André Mignot (CHV), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Myeloid, CD34, Chronic myelomonocytic leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Humans, Cell Proliferation, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, hemic and immune systems, Hematology, Dendritic Cells, medicine.disease, 3. Good health, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Phenotype, RUNX1, chemistry, 030220 oncology & carcinogenesis, Mutation, Cancer research, Interleukin-3 receptor, CD5, 030215 immunology
Abstract

Neoplasms involving plasmacytoid dendritic cells (pDC) include blastic pDC neoplasms (BPDCN) and other pDC proliferations, where pDC are associated with myeloid malignancies: most frequently chronic myelomonocytic leukemia (CMML) but also acute myeloid leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDC in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DC (cDC) associated in the same sample, by phenotypic and molecular analyses (targeted next-generation sequencing, 70 genes). We compared 15 pDCAML at diagnosis with 21 BPDCN and 11 normal pDC from healthy donors. CD45low CD34+ blasts were found in all cases (10-80% of medullar cells), associated with pDC (4-36%), monocytes in 14 cases (1-10%) and cDC (two cases, 4.8-19%). pDC in pDC-AML harbor a clearly different phenotype from BPDCN: CD4+ CD56– in 100% of cases, most frequently CD303+, CD304+ and CD34+; lower expression of cTCL1 and CD123 with isolated lymphoid markers (CD22/CD7/CD5) in some cases, suggesting a prepDC stage. In all cases, pDC, monocytes and cDC are neoplastic since they harbor the same mutations as CD34+ blasts. RUNX1 is the most commonly mutated gene: detected in all AML with minimal differentiation (M0-AML) but not in the other cases. Despite the low number of cases, the systematic association between M0-AML, RUNX1 mutations and an excess of pDC is puzzling. Further evaluation in a larger cohort is required to confirm RUNX1 mutations in pDC-AML with minimal differentiation and to investigate whether it represents a proliferation of blasts with macrophage and DC progenitor potential.

Published
2020
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10. Localisations cutanées d’un lymphome lymphoblastique T

Author

F. Comoz, Sylvain Chantepie, C. Brugière, L. Verneuil, C. Nascimbeni, and Véronique Salaun

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Dermatology
Abstract

Resume Introduction Le lymphome lymphoblastique (LBL) est un lymphome non hodgkinien (LNH) rare. Les localisations cutanees des LBL concernent moins de 20 % des patients. Observation Nous rapportons le cas d’un homme de 66 ans sans antecedent pathologique notable qui presentait une lesion tumorale du cuir chevelu d’extension progressive, plusieurs macules et nodules violaces du tronc ainsi qu’une adenopathie spinale unique. La tomodensitometrie (TDM) thoraco-abdomino-pelvienne, realisee en raison d’une insuffisance renale aigue, montrait une importante infiltration tissulaire retroperitoneale. Les biopsies cutanees et le bilan d’extension concluaient a un LBL-T associant des lesions cutanees, osseuses et ganglionnaires retroperitoneales, sans masse mediastinale. Apres deux mois de traitement par CHOP (quatre cycles), les lesions cutanees et la masse tumorale abdominale avaient regresse, et la fonction renale etait revenue a la normale. Discussion Treize cas de LBL avec atteinte cutanee ont ete rapportes ; la plupart des patients etaient jeunes (moins de 30 ans) et presentaient des lesions cutanees multiples (nodules ou tumeurs) associees a de nombreuses adenopathies peripheriques, un envahissement de la moelle osseuse et souvent une masse mediastinale. La presentation clinique du LBL-T dans notre cas est originale en raison des localisations cutanees associees a un syndrome tumoral abdominal, sans infiltration mediastinale, avec une adenopathie peripherique unique, chez un sujet âge.

Published
2017
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12. The prognostic value of hematogones in patients with acute myeloid leukemia

Author

Anne-Claire Gac, Véronique Salaun, Gandhi Damaj, Khaled Benabed, Jean-Pierre Vilque, Sylvain Chantepie, Oumedaly Reman, Jean-Jacques Parienti, Margaret Macro, Hyacinthe Johnson-Ansah, and Stéphane Cheze

Subjects
Oncology, medicine.medical_specialty, Myeloid, Performance status, business.industry, Induction chemotherapy, Myeloid leukemia, Hematology, medicine.disease, Minimal residual disease, 03 medical and health sciences, Leukemia, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Internal medicine, Immunology, medicine, Bone marrow, business, Survival analysis, 030215 immunology
Abstract

In acute myeloid leukemia (AML), new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B-lymphocyte precursors that increase in hematological diseases and may influence remission duration in AML. HG detection was prospectively investigated in 262 AML patients to determine its prognostic value. Flow cytometric HG detection was performed in bone marrow aspiration after intensive chemotherapy at the time of hematological recovery. Patients with HGs in bone marrow samples had a significantly better relapse-free survival (RFS) and overall survival (OS) than patients without HGs (P = 0.0021, and P = 0.0016). Detectable HGs independently predicted RFS (HR = 0.61, 95%CI: 0.42 - 0.89, P = 0.012) and OS (HR = 0.59, 95%CI: 0.38 - 0.92, 0.019) controlling for age, ELN classification, the number of chemotherapy cycles to achieve CR, performance status, secondary AML and flow cytometric minimal residual disease (MRD). In intensively treated AML, individual determination of HGs could be useful to stratify the optimal risk-adapted therapeutic strategy after induction chemotherapy. Am. J. Hematol. 91:566-570, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016
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13. Standardization of Flow Cytometric Immunophenotyping for Hematological Malignancies: The FranceFlow Group Experience

Author

Carmen Mariana Aanei, Hind Bennami, Victoria Raggeneau, Chantal Brouzes, Françoise Solly, Lydia Campos, Amélie Trinquand, Nicolas Neyman, Ludovic Lhermitte, Vahid Asnafi, Caroline Mayeur-Rousse, Agathe Debliquis, Anne Roggy, Frédéric Massin, Adriana Plesa, Myrto Costopoulos, Anne-Catherine Lhoumeau, Hugues Jacqmin, Fanny Angelot-Delettre, Soraya Wuilleme, Elodie Lainey, Nelly Robillard, Sébastien Lachot, Coralie Derrieux, Lucile Baseggio, Alice Eischen, Francine Garnache-Ottou, Alessandra Rosenthal-Allieri, Mickael Roussel, Hubert Rambaud, Elisabeth Andre-Kerneis, Christine Arnoulet, Magali Le Garff-Tavernier, Véronique Salaun, Michel Ticchioni, Edouard Cornet, Marie-Thérèse Georget, Franck Geneviève, Marie-Christine Jacob, Véronique Latger-Cannard, Maxime Maurer, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Département de pharmacie

Subjects
0301 basic medicine, Quality Control, medicine.medical_specialty, Histology, Standardization, quality controls, Fluorescence, Monocytes, Pathology and Forensic Medicine, Immunophenotyping, 03 medical and health sciences, 0302 clinical medicine, Belgium, immunophenotyping, EuroFlow, Internal medicine, medicine, Humans, Lymphocytes, Protocol (science), standardization, Reproducibility, business.industry, hematology, flow cytometry, Reproducibility of Results, Cell Biology, Reference Standards, Flow Cytometry, Clinical trial, 030104 developmental biology, instrument settings, 030220 oncology & carcinogenesis, Hematologic Neoplasms, France, FranceFlow, business, Cytometry, Companion diagnostic
Abstract

Flow cytometry is broadly used for the identification, characterization, and monitoring of hematological malignancies. However, the use of clinical flow cytometry is restricted by its lack of reproducibility across multiple centers. Since 2006, the EuroFlow consortium has been developing a standardized procedure detailing the whole process from instrument settings to data analysis. The FranceFlow group was created in 2010 with the intention to educate participating centers in France about the standardized instrument setting protocol (SOP) developed by the EuroFlow consortium and to organise several rounds of quality controls (QCs) in order to evaluate the feasibility of its application and its results. Here, we report the 5 year experience of the FranceFlow group and the results of the seven QCs of 23 instruments, involving up to 19 centers, in France and in Belgium. The FranceFlow group demonstrates that both the distribution and applicability of the SOP have been successful. Intercenter reproducibility was evaluated using both normal and pathological blood samples. Coefficients of variation (CVs) across the centers were

Published
2019

14. Usefulness of Flow Cytometry for the Detection of Cutaneous Localization in Malignant Hematologic Disorders

Author

Edouard Cornet, Véronique Salaun, Gandhi Damaj, F. Comoz, Elsa Maitre, Anne-Laure Le-Page, Xavier Troussard, Florence Truquet, Laurence Verneuil, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Male, Pathology, medicine.medical_specialty, skin, Histology, Skin Neoplasms, Dipeptidyl Peptidase 4, Pathology and Forensic Medicine, Flow cytometry, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Biopsy, medicine, Humans, biopsy, Aged, CD26, Mycosis fungoides, Myeloproliferative Disorders, medicine.diagnostic_test, integumentary system, business.industry, Cell Biology, Middle Aged, medicine.disease, Flow Cytometry, 3. Good health, Lymphoma, 030104 developmental biology, 030220 oncology & carcinogenesis, Hematologic Neoplasms, Sézary syndrome, Skin biopsy, mycosis Fungoides, Neoplastic cell, Immunohistochemistry, Female, business, Cytometry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Histological evaluation of malignant hematologic involvement of the skin can be challenging and needs an extended immunohistochemistry panel. We assessed the ability of flow cytometry (FCM) to detect neoplastic cell subsets in skin biopsies as a useful tool that supplements the histological examination in a complementary way. Methods Two hundred and forty-three consecutive skin biopsies were retrospectively analyzed between April 2012 and July 2017. Results Among them, 147 samples, corresponding to 128 patients, were analyzed at diagnosis. Eighty-seven patients had erythrodermic inflammatory dermatoses, and 41 patients had cutaneous hematologic neoplasms. Cutaneous T-cell lymphomas were the most frequent disorders, accounting for 70% of cases (29/41). Cutaneous B-cell lymphoma was found in only 17% of cases (7/41) and immature hematologic malignancies in 5% (2/41). Three patients had secondary skin involvement. The sensitivity of FCM skin biopsy analysis was 78.1% (32/41). Among the 243 samples, 27 patients had mycosis fungoides (MF) or Sezary syndrome (SS) with available FCM data. A loss of CD26 expression was identified in 92% of cases of transformed MF or SS versus 40% of cases of non-transformed MF (P = 0.0057 χ²). Among the 12 MF patients with negative CD26 expression, six progressed to SS versus none in the positive group (50% vs. 0% P = 0.0168 χ²). Conclusions FCM analysis of the skin biopsies is a sensitive method and a useful tool for improving the sensitivity of diagnosis of hematologic skin neoplasms. Among the MF patients, a loss of CD26 expression could be a marker of higher risk of progression. © 2019 International Clinical Cytometry Society.

Published
2019
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15. Hairy cell leukemia and unusual pleural location

Author

Ouda Ghoual, Véronique Salaun, Edouard Cornet, Thomas Hueso, Xavier Troussard, and Dina Naguib

Subjects
business.industry, medicine, Hairy cell leukemia, Hematology, medicine.disease, business, Molecular biology
Abstract

La leucemie a tricholeucocytes (HCL) est une hemopathie maligne rare. Des localisations inhabituelles de la maladie sont parfois observees mais restent rares. Nous rapportons l’observation d’un patient atteint de HCL traite par interferon, qui developpe au cours de sa maladie une masse mediastinopleurale decouverte de facon fortuite apres un traumatisme. Cette masse fait discuter une origine traumatique, infectieuse, cancereuse ou une localisation specifique de la maladie. Le diagnostic de localisation specifique est retenu. Le traitement par la cladribine est efficace, permettant de faire regresser et de faire disparaitre la lesion.

Published
2015
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16. Leucémie aiguë promyélocytaire : à propos d’un cas clinique

Author

Michèle Malet, Xavier Troussard, Ouda Ghoual, Véronique Salaun, Stéphanie Jouve, and Thomas Hueso

Subjects
Medical Laboratory Technology, Biochemistry (medical), Analytical Chemistry
Abstract

Monsieur N…, 33 ans, est hospitalise en hematologie en 2013 pour la prise en charge d’une leucemie aigue. Il a comme antecedents une pancreatite aigue dans un contexte d’alcoolisation aigue et une cholecystectomie pour lithiases vesiculaires. A l’examen clinique, le patient presente une fievre a 38,6 °C, un syndrome hemorragique avec des ecchymoses recentes sur les avant-bras et les jambes et une hypertrophie amygdalienne droite. Il n’existe ni adeno-pathie palpable, ni d’hepato-splenomegalie.Les resultats de l’hemogramme sont les suivants : hematies : 2,21 T/L, hemoglobine : 6,6 g/dL, VGM : 92,9 fl, CCMH : 33,8 g/dl, reticulocytes : 62 G/L, plaquettes : 21 G/L, leu-cocytes : 5,38 G/L (polynucleaires neutrophiles : 0,16 G/L, polynucleaires eosinophiles : 0,11 G/L, polynucleaires baso-philes : 0,05 G/L, lymphocytes : 1,61 G/L et monocytes : 0,11 G/L). L’examen du frottis sanguin colore au May-Grunwald-Giemsa (MGG) montre la presence de 60 % de blastes avec un noyau bilobe en aile de papillon evoquant des promyelocytes anormaux, certains ont des corps d’Auer en fagots dans le cytoplasme. A noter l’absence de schi-zocytes et d’amas plaquettaires. Le myelogramme met en evidence une moelle infiltree avec 74 % de blastes dystro-phiques avec un noyau nucleole, bilobe en aile de papillon, un cytoplasme tres granuleux avec presence de nombreux corps d’Auer parfois disposes en fagots a la coloration au MGG

Published
2015
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17. Increased frequencies of circulating and tumor-resident Vδ1 T cells in patients with diffuse large B-cell lymphoma

Author

Kathy Khoy, Khaled Benabed, Christophe Fruchart, Anne-Dominique Pham, Anne-Claire Gac, Oumedaly Reman, Véronique Salaun, Emilie Reboursiere, Sylvain Chantepie, Jean-Baptiste Mear, Stéphane Cheze, Margaret Macro, Xavier Troussard, Olivier Toutirais, Gandhi Damaj, Quentin Cabrera, Jean-Pierre Vilque, Hyacinthe Johnson-Ansah, Anthony Garnier, Brigitte Le Mauff, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Sérine protéases et physiopathologie de l'unité neurovasculaire, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), and Université de Rouen Normandie (UNIROUEN)

Subjects
0301 basic medicine, Cancer Research, T cell, diffuse large B-cell lymphoma, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, medicine, Cytotoxic T cell, CD40, biology, CD28, Germinal center, Hematology, Natural killer T cell, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, cancer immunosurveillance, Oncology, Gamma-delta T cells, Immunology, biology.protein, Interleukin 12, immunotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract

Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1+ T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1+ T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells. While circulating Vδ1+ T cells of patients or HSs mostly exhibited a naive phenotype, the majority of tumor Vδ1+ T cells showed a central memory phenotype. Resident or circulating γδ T cells from patients were not functionally impaired since they produced high levels of IFN-γ. Collectively, our findings are in favor of γδ T cell activation in tumors and open new perspectives for their modulation in DLBCL immunotherapy.

Published
2018
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18. New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes

Author

Pierre-Julien Viailly, Edouard Cornet, Brigitte Sola, Xavier Troussard, Elsa Maitre, Margaux Wiber, Fabrice Jardin, Véronique Salaun, Dina Naguib, Philippe Bertrand, Catherine Maingonnat, Gandhi Damaj, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Registre des hémopathies malignes de Basse-Normandie [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), BOUAKAZ, Amel, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)

Subjects
0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Gene mutation, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, hairy cell leukemia, Hairy cell leukemia, Epigenetics, gene mutation, Allele frequency, Gene, Exome sequencing, epigenetic regulation genes, Hairy Cell Leukemia Variant, Mutation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], next-generation sequencing, hairy cell leukemia variant, Research Paper
Abstract

International audience; Classical hairy cell leukemia (HCL-c) is a rare lymphoid neoplasm. BRAFV600E mutation, detected in more than 80% of the cases, is described as a driver mutation, but additional genetic abnormalities appear to be necessary for the disease progression. For cases of HCL-c harboring a wild-type BRAF gene, the differential diagnosis of the variant form of HCL (HCL-v) or splenic diffuse red pulp lymphoma (SDRPL) is complex. We selected a panel of 21 relevant genes based on a literature review of whole exome sequencing studies (BRAF, MAP2K1, DUSP2, MAPK15, ARID1A, ARID1B, EZH2, KDM6A, CREBBP, TP53, CDKN1B, XPO1, KLF2, CXCR4, NOTH1, NOTCH2, MYD88, ANXA1, U2AF1, BCOR, and ABCA8). We analyzed 20 HCL-c and 4 HCL-v patients. The analysis of diagnostic samples mutations in BRAF (n = 18), KLF2 (n = 4), MAP2K1 (n = 3), KDM6A (n = 2), CDKN1B (n = 2), ARID1A (n = 2), CREBBP (n = 2) NOTCH1 (n = 1) and ARID1B (n = 1). BRAFV600E was found in 90% (18/20) of HCL-c patients. In HCL-c patients with BRAFV600E , other mutations were found in 33% (6/18) of cases. All 4 HCL-v patients had mutations in epigenetic regulatory genes: KDM6A (n = 2), CREBBP (n = 1) or ARID1A (n = 1). The analysis of sequential samples (at diagnosis and relapse) from 5 patients (2 HCL-c and 3 HCL-v), showed the presence of 2 new subclonal mutations (BCORE1430X and XPO1E571K ) in one patient and variations of the mutated allele frequency in 2 other cases. In the HCL-v disease, we described new mutations targeting KDM6A that encode a lysine demethylase protein. This opens new perspectives for personalized medicine for this group of patients.

Published
2018
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19. Gemtuzumab ozogamicin in combination with intensive chemotherapy in relapsed or refractory acute myeloid leukemia

Author

Sylvain Chantepie, Margaret Macro, Emilie Reboursiere, Jean-Baptiste Mear, Stéphane Cheze, Oumedaly Reman, Khaled Benabed, Véronique Salaun, Jean-Pierre Vilque, Hyacinthe Johnson-Ansah, and Anne-Claire Gac

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Gemtuzumab ozogamicin, Salvage therapy, Antibodies, Monoclonal, Humanized, Gastroenterology, Young Adult, European LeukemiaNet, Refractory, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Salvage Therapy, Response rate (survey), business.industry, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Middle Aged, Prognosis, Gemtuzumab, Survival Analysis, Confidence interval, Surgery, Leukemia, Myeloid, Acute, Aminoglycosides, Treatment Outcome, Oncology, Toxicity, Female, business, medicine.drug
Abstract

The prognosis of refractory/relapsed acute myeloid leukemia (AML) remains poor. The complete response (CR) rate after relapse is around 25%, with 11% of patients still alive after 5 years. The efficacy and toxicity of fractionated gemtuzumab ozogamicin (fGO; 3 mg/m2, days 1, 4, 7) in combination with intensive chemotherapy were retrospectively evaluated in patients with refractory/relapsed AML. Thirty-six patients (median age 54 years) were included. European LeukemiaNet classification was as follows: favorable (n=6), intermediate-I (n=13), intermediate-II (n=8), adverse (n=9). Median CR duration was 7.16 months (1.63-96.8). The overall response rate was 38.8%, with CR in eight patients (22.2%) and CR with incomplete platelet recovery (CRp) in six patients (16.7%). Two-year overall survival was 26% (95% confidence interval [CI]: 12-42) and 2-year relapse free-survival was 18.5% (95% CI: 6.6-35.0). Salvage therapy with fractionated GO in patients with very high-risk disease produced a 38.8% response rate and may be considered as a bridge therapy to transplant.

Published
2015
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20. Increased frequencies of circulating and tumor-resident Vδ1

Author

Emilie, Reboursiere, Anne-Claire, Gac, Anthony, Garnier, Véronique, Salaun, Oumedaly, Reman, Anne-Dominique, Pham, Quentin, Cabrera, Kathy, Khoy, Jean-Pierre, Vilque, Christophe, Fruchart, Sylvain, Chantepie, Hyacinthe, Johnson-Ansah, Margaret, Macro, Stéphane, Cheze, Khaled, Benabed, Jean-Baptiste, Mear, Xavier, Troussard, Gandhi, Damaj, Brigitte, Le Mauff, and Olivier, Toutirais

Subjects
Adult, Aged, 80 and over, Male, Receptors, Antigen, T-Cell, gamma-delta, Middle Aged, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating, T-Lymphocyte Subsets, Cytokines, Humans, Female, Immunotherapy, Lymphocyte Count, Lymphoma, Large B-Cell, Diffuse, Immunologic Memory, Immunologic Surveillance, Aged, Neoplasm Staging
Abstract

Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1

Published
2017

21. Flow cytometry minimal residual disease after allogeneic transplant for chronic lymphocytic leukemia

Author

Dominique Bories, Veronique Leblond, Magali Le Garff-Tavernier, Mauricette Michallet, Oumedaly Reman, Caroline Algrin, Marie-Christine Béné, Olivier Tournilhac, Nathalie Dhedin, Véronique Salaun, Adriana Plesa, Anne Huynh, Jean-Louis Golmard, Aurore Perrot, Anne Sirvent, Hélène Merle-Béral, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Henri Mondor, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hematology Laboratory, Hospices Civils de Lyon, Archéologie et Philologie d'Orient et d'Occident (AOROC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Hématologie moléculaire [CHU Mondor], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Henri Mondor [Créteil], Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département des Sciences de l'Antiquité - ENS Paris (DSA ENS-PSL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de biostatistiques et information médicale [CHU Pitié-Salpêtrière], Paris Sciences et Lettres (PSL)-École normale supérieure - Paris (ENS Paris)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [APHP], and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Oncology, Male, medicine.medical_specialty, Allogeneic transplantation, Neoplasm, Residual, medicine.medical_treatment, Chronic lymphocytic leukemia, Hematopoietic stem cell transplantation, Disease-Free Survival, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Survival rate, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, General Medicine, Middle Aged, medicine.disease, Allografts, Flow Cytometry, Minimal residual disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, body regions, Transplantation, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Immunology, Female, Stem cell, business, 030215 immunology
Abstract

Objectives This study investigates whether achieving complete remission (CR) with undetectable minimal residual disease (MRD) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL) affects outcome. Methods We retrospectively studied 46 patients transplanted for CLL and evaluated for post-transplant MRD by flow cytometry. Results At transplant time, 43% of the patients were in CR, including one with undetectable MRD, 46% were in partial response, and 11% had refractory disease. After transplant, 61% of the patients achieved CR with undetectable MRD status. By multivariate analysis, reaching CR with undetectable MRD 12 months after transplant was the only factor associated with better progression-free survival (P = 0.02) and attaining undetectable MRD, independently of the time of negativity, was the only factor that correlated with better overall survival (P = 0.04). Conclusion Thus, achieving undetectable MRD status after allo-SCT for CLL is a major goal to improve post-transplant outcome.

Published
2017
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22. An unusual Sézary syndrome with concomitant pulmonary localization: aggressiveness of folliculotropic form

Author

Sylvain Chantepie, A. Stefan, F. Comoz, Karine Campbell, Charlotte Brugière, Véronique Salaun, and L. Verneuil

Subjects
Male, Pathology, medicine.medical_specialty, Lung Neoplasms, Skin Neoplasms, business.industry, Biopsy, Needle, Dermatology, Middle Aged, Immunohistochemistry, Risk Assessment, 030207 dermatology & venereal diseases, 03 medical and health sciences, Fatal Outcome, 0302 clinical medicine, 030220 oncology & carcinogenesis, Concomitant, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Humans, Sezary Syndrome, Medicine, Neoplasm Invasiveness, business, Neoplasm Staging
Published
2014
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23. Vasculitis associated with large granular lymphocyte (LGL) leukemia: Presentation and treatment outcomes of 11 cases

Author

Stéphane Cheze, Boris Bienvenu, Loïk Geffray, Estibaliz Lazaro, Felipe Suarez, Véronique Salaun, Jonathan Boutemy, Flore Sicre, Nicolas Schleinitz, Cindy Castrale, Magaret Macro, Jerome Rey, Florence Truquet, Loïc Guillevin, Benoit Bareau, Alexandra Audemard, Thierry Lobbedez, Thierry Lamy, and Laurence Verneuil

Subjects
Adult, Male, Vasculitis, medicine.medical_specialty, Pathology, Population, chemical and pharmacologic phenomena, Gastroenterology, Rheumatology, Internal medicine, medicine, Humans, education, Glucocorticoids, Peripheral neuritis, Aged, education.field_of_study, business.industry, Middle Aged, medicine.disease, Cutaneous leukocytoclastic angiitis, Leukemia, Large Granular Lymphocytic, Leukemia, Purpura, Giant cell arteritis, Treatment Outcome, Anesthesiology and Pain Medicine, Female, medicine.symptom, business, Microscopic polyangiitis, Immunosuppressive Agents
Abstract

The association between vasculitis and large granular lymphocyte (LGL) leukemia has rarely been reported or investigated. Thus, we assessed the clinical and biological phenotypes of LGL leukemia associated with vasculitis.We studied a series of 11 patients displaying LGL leukemia associated with vasculitis (LAV). The mean age at diagnosis of LGL leukemia was 60.3 years; there were nine women and two men. The mean follow-up period was 45 months. The main LGL lineage was T-LGL (10 patients), and only one NK-LGL was identified. Clinical and biological features of T-LGL leukemia were compared with those from the 2009 French T-LGL registry. We did not find any relevant differences except that patients with LAV were predominantly female (p0.05). The most frequently observed vasculitis was cryoglobulinemia (n = 5). Three patients presented with cutaneous leukocytoclastic angiitis, two patients had ANCA-negative microscopic polyangiitis, and one patient had giant cell arteritis. The main clinical features involved the skin, e.g., purpura (91%), arthralgia (37%), peripheral neuritis (27%), and renal glomerulonephritis (18%). The most frequent histologic finding was leucocytoclastic vasculitis (54%). The rate of complete remission was high; i.e., 80%. A minority of patients had a vasculitis relapse (27%). Three patients (27%) died; one death was related to LGL leukemia (acute infection) and the two other deaths were related to vasculitis (both with heart failure).We conclude that vasculitis is overrepresented in the population of LGL patients, LAV predominantly affects women, vasculitis preferentially affects the small vessels, and LAV has high rate of complete response.

Published
2013
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24. Mitochondrial DNA Alterations and Oxidative Stress in Acute Leukemia

Author

Mouna Saadaoui, Stéphane Allouche, Lamia Aissaoui, Mohamed Manai, and Véronique Salaun

Subjects
Mitochondrial DNA, Leukemia, Acute leukemia, Germline mutation, Cancer cell, medicine, TFAM, Biology, medicine.disease_cause, medicine.disease, Carcinogenesis, Molecular biology, Oxidative stress
Abstract

Mitochondrial DNA (mtDNA) alterations were reported in many cancers but their roles in oncogenesis are still debated. We aimed to examine qualitative and quantitative mtDNA modifications and oxidative stress in normal and cancer cells. 23 leukemia patients and 18 healthy subjects were recruited from the hospital of Azziza Othmana (Tunisia). Mitochondrial D-loop was sequenced, mtDNA level was determined by Q-PCR, the oxidative stress was assessed by a fluorescent probe and the mitochondrial transcription factor A (mTFA) level was quantified. No somatic mutation was evidenced in leukemia cells compared to non-malignant cells. However, a significant higher level of mtDNA associated with an increase of mTFA expression and reactive oxygen species (ROS) production were measured in patients' cells compared to non-malignant cells. In conclusion, our results don't support the role of mtDNA mutations in leukemogenesis but increase of mtDNA and ROS levels would be molecular signatures of leukemia.

Published
2013
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25. IgM multiple myeloma: a particular disease?

Author

Xavier Troussard, Véronique Salaun, Sylvain Chantepie, Magaret Macro, and Quentin Cabrera

Subjects
media_common.quotation_subject, medicine, Ethnology, Hematology, Art, medicine.disease, Humanities, Multiple myeloma, media_common
Abstract

hma.2011.0624 Auteur(s) : Quentin Cabrera1 Cabrera-q@chu-caen.fr, Sylvain Chantepie1, Veronique Salaun2, Xavier Troussard2, Magaret Macro1 1 Service d’hematologie clinique 2 Service d’hematologie biologique, CHU de Caen, 14033 Caen Cedex 9 Tires a part : Q. Cabrera La presence d’une IgM monoclonale serique est souvent associee au diagnostic de macroglobulinemie de Waldenstrom (MW) ou a d’autres syndromes lymphoproliferatifs chroniques B (SLPC-B), comme la leucemie lymphoide [...]

Published
2011
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27. The prognostic value of hematogones in patients with acute myeloid leukemia

Author

Sylvain P, Chantepie, Jean-Jacques, Parienti, Véronique, Salaun, Khaled, Benabed, Stéphane, Cheze, Anne-Claire, Gac, Hyacinthe, Johnson-Ansah, Margaret, Macro, Gandhi, Damaj, Jean-Pierre, Vilque, and Oumedaly, Reman

Subjects
Adult, Aged, 80 and over, Male, Adolescent, Precursor Cells, B-Lymphoid, Middle Aged, Flow Cytometry, Prognosis, Risk Assessment, Survival Analysis, Disease-Free Survival, Cohort Studies, Leukemia, Myeloid, Acute, Young Adult, Bone Marrow, Recurrence, Humans, Female, Lymphocyte Count, Aged
Abstract

In acute myeloid leukemia (AML), new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B-lymphocyte precursors that increase in hematological diseases and may influence remission duration in AML. HG detection was prospectively investigated in 262 AML patients to determine its prognostic value. Flow cytometric HG detection was performed in bone marrow aspiration after intensive chemotherapy at the time of hematological recovery. Patients with HGs in bone marrow samples had a significantly better relapse-free survival (RFS) and overall survival (OS) than patients without HGs (P = 0.0021, and P = 0.0016). Detectable HGs independently predicted RFS (HR = 0.61, 95%CI: 0.42 - 0.89, P = 0.012) and OS (HR = 0.59, 95%CI: 0.38 - 0.92, 0.019) controlling for age, ELN classification, the number of chemotherapy cycles to achieve CR, performance status, secondary AML and flow cytometric minimal residual disease (MRD). In intensively treated AML, individual determination of HGs could be useful to stratify the optimal risk-adapted therapeutic strategy after induction chemotherapy. Am. J. Hematol. 91:566-570, 2016. © 2016 Wiley Periodicals, Inc.

Published
2016

28. The level of blast CD33 expression positively impacts the effect of gemtuzumab ozogamicin in patients with acute myeloid leukemia

Author

Adrienne de Labarthe, Florent Dumezy, Edouard Cornet, Sylvie Castaigne, Hervé Dombret, Cécile Pautas, Orianne Wagner-Ballon, Estelle Guérin, Jean-Noël Bastie, Xavier Thomas, Emmanuel Raffoux, Guillaume Olombel, Jean Feuillard, Sylvain Chantepie, Julien Guy, Ollivier Legrand, Claude Preudhomme, Adriana Plesa, Jean-Yves Perrot, Véronique Salaun, Pascal Turlure, Cheval, Christelle, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie Biologique (HEGP - Hématologie Biologique), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Lille (CHU de Lille), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire d'hématologie [AP-HP Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'Hématologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie Biologique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Centre Hospitalier de Versailles André Mignot (CHV), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Hématologie Biologique ( HEGP - Hématologie Biologique ), Assistance publique - Hôpitaux de Paris (AP-HP), Centre Hospitalier Universitaire de Lille ( CHU de Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Centre Hospitalier de Versailles (CHV), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Myeloid, Patients, Gemtuzumab ozogamicin, Immunology, CD33, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Calicheamicin, medicine, ComputingMilieux_MISCELLANEOUS, Leukemia, business.industry, Myeloid leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, 3. Good health, Immunoconjugate, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Monoclonal, Cancer research, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, France, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, 030215 immunology, medicine.drug
Abstract

International audience; Gemtuzumab ozogamicin (GO) is an immunoconjugate, combining an anti-CD33 monoclonal antibody to calicheamicin, a highly cytotoxic antibiotic. First developed as single agent in adults with relapsed acute myeloid leukemia (AML), it was then evaluated in combination with chemotherapy in newly diagnosed patients. In the randomized Acute Leukemia French Association (ALFA)–0701 study, we reported that sequential administration of a lower dose of GO allowed the safe delivery of a high cumulative dose associated with a substantial improvement in patient outcome. A recent meta-analysis has confirmed that adding GO to chemotherapy may provide a survival advantage in patients without adverse cytogenetic characteristics. However, these results were obtained regardless of the level of blast CD33 expression. In vitro, a clear relationship between CD33 expression and GO efficacy has nevertheless been shown. In vivo, contradictory results have been reported so far. No impact was found when CD33 expression was evaluated as a continuous covariable or using a 20% cutoff. Higher response rates were nevertheless reported for patients with CD33+ expression ≥98% in 1 phase 2 study or when showing CD33 expression as mean fluorescence intensity (MFI) using an isotype antibody as control. To further evaluate the impact of CD33 expression on GO treatment effect, we retrospectively analyzed the results of the ALFA-0701 study.

Published
2016
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29. La leucémie aiguë peu différenciée (MO) aspects hématologiques, immunophénotypiques, cytogénétiques, incidence pronostique

Author

Xavier Troussard, Michèle Malet, Ghislaine Plessis, Dina Naguib, Sophie Bustanya, and Véronique Salaun

Subjects
Medical Laboratory Technology, Biochemistry (medical), Analytical Chemistry
Abstract

Resume La LAMO ou leucemie aigue peu differenciee represente 6 a 10 % des LAM. Elle a ete decrite chez des patients de tout âge mais son incidence reste nettement plus elevee chez les personnes âgees. Le diagnostic repose sur l'etude morphologique des blastes, sur la negativite des reactions cytochimiques et sur leur analyse en cytometrie en flux afin de confirmer leur appartenance a la lignee myeloide. Aucune anomalie genetique specifique des LAM0 n'a encore ete decouverte mais certaines sont plus frequentes dans ce type de pathologie (trisomies 8 et 13, monosomies 5 et 7, anomalies du chromosome 11). Le devenir clinique des patients est particulierement sombre avec une mortalite a 1 an superieure a 50 %, s'exptiquant par I'accumulation de facteurs de mauvais pronostic. Une recherche des modifications cellulaires responsables de cette proliferation myeloide permettrait sans doute d'ameliorer la prise en charge de la maladie et faciliterait la decouverte de nouveaux traitements.

Published
2007
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30. 18F-FDG PET/CT in Hepatosplenic Gamma-Delta T-Cell Lymphoma

Author

Elske Quak, Cécile Le Naourès, Christophe Fruchart, and Véronique Salaun

Subjects
medicine.medical_specialty, Lymphoma, T-Cell, Multimodal Imaging, X ray computed, Fluorodeoxyglucose F18, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Ct findings, Multimodal imaging, medicine.diagnostic_test, business.industry, Splenic Neoplasms, Liver Neoplasms, food and beverages, General Medicine, Middle Aged, medicine.disease, Lymphoma, Renal transplant, Positron emission tomography, Hepatosplenic Gamma/Delta T-Cell Lymphoma, Positron-Emission Tomography, Fdg pet ct, Female, Radiology, Radiopharmaceuticals, business, Tomography, X-Ray Computed
Abstract

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and often difficult-to-diagnose subtype of lymphoma that can occur in the chronically immunosuppressed patient. We present the typical FDG PET/CT findings of HSTCL in a renal transplant recipient. The whole-body metabolic and morphologic information provided by FDG PET/CT can be of great additional value in establishing this diagnosis, thus allowing for a timely start of treatment.

Published
2015

31. Unusual Extramedullary Plasmacytoma: A Rare but Possible Cause of Lymphadenopathy in Chronic Lymphocytic Leukemia

Author

E. Lechapt-Zalcman, Véronique Salaun, Margaret Macro, Sylvain Chantepie, Jean-Baptiste Mear, Quentin Cabrera, Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), and Département de Pathologie [CHU Caen]

Subjects
Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, medicine.medical_treatment, Lymph node biopsy, lcsh:Medicine, Aggressive lymphoma, Case Report, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Medicine, Lymph node, neoplasms, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, lcsh:R, General Medicine, medicine.disease, 3. Good health, Natural history, Radiation therapy, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Concomitant, business, Adenectomy
Abstract

International audience; Cervical bilateral lymphadenopathy is a frequent event during chronic lymphocytic leukemia (CLL) natural history. However, lymph node biopsy is generally not required as long as transformation into an aggressive lymphoma (Richter syndrome) is not suspected. We present here a rare case of CLL patient who developed progressive bilateral cervical lymph node and bilateral tonsillar hypertrophy. CLL front-line therapy was ineffective leading to adenectomy and diagnosis of concomitant extramedullary plasmacytoma. Radiotherapy did not result in the disappearance of lymphadenopathy. Adenectomy should be performed in CLL cases to avoid misdiagnosis.

Published
2015
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32. Deciphering leukemic B-cell chronic lymphoproliferative disorders

Author

Isabelle Radford-Weiss, Chantal Brouzes, Rémi Letestu, M. Guesnu, Florence Ajchenbaum-Cymbalista, Vincent Levy, Valérie Ugo, Françoise Valensi, Nathalie Leporrier, Sylvie Ramond, Jean-Yves Perrot, Joelle Nataf, Françoise Picard, Véronique Salaun, and Xavier Troussard

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Pathology, Lymphoma, B-Cell, Chronic lymphocytic leukemia, Lymphoproliferative disorders, CD5 Antigens, Immunophenotyping, Cohort Studies, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Cyclin D1, Prospective Studies, B cell, Aged, CD20, Hematology, biology, business.industry, Cell Cycle, Middle Aged, Antigens, CD20, Prognosis, medicine.disease, Lymphoproliferative Disorders, Lymphoma, medicine.anatomical_structure, biology.protein, Female, CD5, business, Cyclin-Dependent Kinase Inhibitor p27
Abstract

Diagnosis of leukemic B-cell chronic lymphoproliferative disorders (B-CLPD) is a frequent challenge in hematology. In this multicentric study, we prospectively studied 165 new consecutive leukemic patients with B-CLPD selected on the basis of Royal Marsden Hospital scoring system < or =3. The primary aim of the study was to try to decipher the atypical cases and identify homogenous subgroups. Overall, morphological examination contributed to diagnosis in only 20% cases, all of them CD5 negative. Thirty additional cases were CD5 negative suggestive of leukemic marginal zone lymphoma in most cases. The significantly poorer survival of the 26 cyclin D1 positive cases justifies recommending its systematic determination among atypical B-CLPD. CD20 expression segregated clearly two subgroups among CD5 positive cyclin D1 negative B-CLPD. The 17 patients with the CD20 dim profile represent a homogeneous subgroup very close to typical B-cell chronic lymphocytic leukemia (B-CLL) on morphological, phenotypical and cytogenetical criteria. In contrast, the subgroup of 51 patients with a CD20 bright profile is heterogeneous. Their significantly lower p27 expression level suggest the presence of a proliferative component, underlying a more aggressive disease. Further genomic studies are warranted to establish their precise nature. These cases should not be included in the same therapeutic trials as B-CLL.

Published
2006
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34. Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells

Author

Jacqueline Poulet, Marie-Christine Jacob, Eric Deconinck, Christophe Ferrand, Emilienne Kuhlein, Pierre Tiberghien, Jean-Claude Bensa, Françoise Schillinger, Bernard Drenou, Sabeha Biichle, Patrick Darodes de Tailly, Laurence Chaperot, Jean-Paul Remy-Martin, Véronique Salaun, Francine Garnache-Ottou, Estelle Seilles, Bénédicte Bulabois, Joel Plumas, Philippe Saas, Michel Arock, Hôpital Michallon, Laboratoire recherche et développement, EFS, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de biologie moléculaire, Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Electrical and Computer Engineering department, James Cook University (JCU), Bases moléculaires de la progression tumorale -Groupe de Recherche sur les Lymphomes, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR73, Laboratoire d'Immunocytologie, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mécanique et d'Acoustique [Marseille] (LMA ), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM), Laboratoires Immunocytologie et HLA, département d'Immunologie Cellulaire, INSERM U823, équipe 9 (Immunobiologie et Immunothérapie des Cancers), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire recherche et développement, EFS-Hôpital Michallon, Etablissement Français du Sang Rhône-Alpes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang Rhône-Alpes, EFS-Laboratoire recherche et développement, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

Subjects
Male, Myeloid, CD3 Complex, MESH: Antigens, CD3, Sialic Acid Binding Ig-like Lectin 3, CD33, MESH: Antigens, CD4, MESH: Flow Cytometry, Plasmacytoid dendritic cell, Biochemistry, Leukemia, Plasma Cell, 0302 clinical medicine, Immunophenotyping, MESH: Antigens, Differentiation, Myelomonocytic, MESH: Antigens, CD, MESH: Aged, MESH: Plasma Cells, 0303 health sciences, Acute leukemia, CD55 Antigens, MESH: Dendritic Cells, hemic and immune systems, Hematology, MESH: Antigens, CD55, Flow Cytometry, 3. Good health, Leukemia, medicine.anatomical_structure, Acute Disease, CD4 Antigens, MESH: Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Leukemia, Plasma Cell, MESH: Immunophenotyping, Plasma Cells, Immunology, Antigens, Differentiation, Myelomonocytic, Biology, 03 medical and health sciences, Antigens, CD, Biomarkers, Tumor, medicine, Humans, Antigen-presenting cell, Aged, 030304 developmental biology, MESH: Humans, Dendritic Cells, Cell Biology, Dendritic cell, medicine.disease, Molecular biology, MESH: Male, MESH: Tumor Markers, Biological, 030215 immunology
Abstract

A new entity of acute leukemia coexpressing CD4(+)CD56(+) markers without any other lineage-specific markers has been identified recently as arising from lymphoid-related plasmacytoid dendritic cells (pDCs). In our laboratory, cells from a patient with such CD4(+)CD56(+) lineage-negative leukemia were unexpectedly found to also express the myeloid marker CD33. To confirm the diagnosis of pDC leukemia despite the CD33 expression, we demonstrated that the leukemic cells indeed exhibited pDC phenotypic and functional properties. In 7 of 8 other patients with CD4(+)CD56(+) pDC malignancies, we were able to confirm that the tumor cells expressed CD33 although with variable expression levels. CD33 expression was shown by flow cytometry, reverse transcriptase-polymerase chain reaction, and immunoblot analysis. Furthermore, CD33 monoclonal antibody stimulation of purified CD4(+)CD56(+) leukemic cells led to cytokine secretion, thus confirming the presence of a functional CD33 on these leukemic cells. Moreover, we found that circulating pDCs in healthy individuals also weakly express CD33. Overall, our results demonstrate that the expression of CD33 on CD4(+)CD56(+) lineage-negative cells should not exclude the diagnosis of pDC leukemia and underline that pDC-specific markers should be used at diagnosis for CD4(+)CD56(+) malignancies.

Published
2004
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35. Leukemic plasmacytoid dendritic cells share phenotypic and functional features with their normal counterparts

Author

Véronique Salaun, Joel Plumas, Francine Brière, Jean-Claude Bensa, Laurence Chaperot, Ivan Perrot, D Blanchard, Marie-Christine Jacob, Véronique Deneys, and Serge Lebecque

Subjects
Adult, Male, Adolescent, T cell, CD40 Ligand, Immunology, Antigen presentation, Immunophenotyping, Antigen, medicine, Humans, Immunology and Allergy, Child, Aged, Aged, 80 and over, CD86, Antigen Presentation, Leukemia, CD40, biology, Cell Differentiation, hemic and immune systems, Dendritic Cells, Middle Aged, Flow Cytometry, Orthomyxoviridae, Phenotype, Cell biology, medicine.anatomical_structure, Antigens, Surface, biology.protein, Cytokines, Female, Interleukin-3, CD80, CD8
Abstract

This work aims to further characterize the newly described leukemic plasmacytoid dendritic cells (LPDC), for which we had previously demonstrated their normal, PDC-like ability to produce IFN-alpha. In addition, LPDC also express the specific antigens BDCA-2 and BDCA-4. Importantly, they become fully competent antigen-presenting cells (APC) after a short maturation induced by IL-3 + CD40L or virus, exhibiting a characteristic APC phenotype (high expression of CD83 and of the costimulatory molecules CD40, CD80, CD86). Whereas IL-3 + CD40L-activated LPDC prime naive CD4(+) T cells towards a Th2 pathway (IL-4-secreting T cells), virus-activated LPDC drive a Th1 profile (IFN-gamma-secreting T cells). Moreover, we show in one case that LPDC are able to capture, process and present exogenous antigens, leading to the activation of both CD4(+) and CD8(+) T cell clones in an antigen-specific manner. This study further characterizes the phenotype and immunological functions of LPDC.

Published
2004
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37. Biological Description of 109 Cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) from the French Network of BPDCN

Author

Bernard Drenou, Sabrina Bouyer, Christophe Ferrand, Anne Galoisy, Francine Garnache Ottou, Christine Arnoulet, Blandine Bénet, Romaric Lacroix, Maïder Pagadoy, Fabrice Jardin, Marie-Christine Béné, Jean Feuillard, Philippe Saas, Chrystelle Vidal, Delphine Binda, Lydia Campos, Michel Ticchioni, Veronique Latger Cannard, Anne Roogy, Françoise Solly, Sylvie Daliphard, Elizabeth Macintyre, Maria Elena Noguera, Franck Geneviève, Françoise Schillinger, Carine Lecoq Lafon, Julien Guy, Valérie Bardet, Eric Deconinck, Anne Arnaud, Sabeha Biichle, Lucile Baseggio, Fanny Angelot Delettre, Liliana Vila, Zehaira Benseddik, Daniel Lusina, Magalie L. E. Garff Tavernier, Christophe Roumier, Véronique Salaun, Vahid Asnafi, Marie Christine Jacob, Eve Poret, Mikael Roussel, Estelle Seilles, Louis Benazet, Adriana Plesa, Veronique Harriverl, Franck Leroux, Jonchère, Laurent, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Clinical Investigation Centre, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Laboratoire de Biologie Médicale, Centre hospitalier de Chartres (Chartres)-Hôpital Louis Pasteur [Chartres], Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hématologie Cellulaire, Hospices Civils de Lyon (HCL), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hematology Laboratory, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biopathology, Haematology Department, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Immunologie, Centre Hospitalier Universitaire de Nice (CHU de Nice)-Groupe hospitalier l'Archet (Nice), Service d'hématologie biologique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie Biologique, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Anatomie et Cytologie Pathologique B, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie - Pathologie, CHU de Saint-Étienne Hôpital Nord (Saint Etienne), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire d'hématologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Laboratoire de biologie médicale, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Ingénierie et biologie cellulaire et tissulaire (IBCT (ex IFR133)), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Université de Franche-Comté ( UFC ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie ( CIC-P803 ), Université de Bourgogne ( UB ) -Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Centre Hospitalier Emile Muller [Mulhouse] ( CH E.Muller Mulhouse ), Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ) -Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire de Nice ( CHU de Nice ) -Groupe hospitalier l'Archet (Nice), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), CHU Angers, Vascular research center of Marseille ( VRCM ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Ingénierie et biologie cellulaire et tissulaire ( IBCT (ex IFR133) ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire d'Hématologie, Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté]), Centre d'Investigation Clinique de Besançon (CICB), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang Bourgogne Franche-Comté-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Universitaire de Nice (CHU Nice)-Groupe hospitalier l'Archet (Nice), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)

Subjects
0303 health sciences, Pathology, medicine.medical_specialty, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Immunology, Cell Biology, Hematology, Blastic plasmacytoid dendritic cell neoplasm, Biology, Biochemistry, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Myeloid cells, medicine, Skin lesion, 030304 developmental biology, 030215 immunology
Abstract

Blastic plasmacytoid dendritic cell neoplasm is a clonal disease derived from precursors of plasmacytoid dendritic cells (pDC). It is a rare neoplasm involving the skin which may or may not be associated from the outset with a leukemic component. The disease invariably progresses to aggressive leukemic dissemination, leading to a differential diagnosis with acute leukemia. In 2004, we set up a French network to recruit biological data at diagnosis. Diagnosis was according to recommendations (Swerdlow et al, 2008), with, in addition, a mandatory panel of pDC markers (Garnache-Ottou et al, 2009) detected by flow cytometry or by immunohistochemistry on infiltrated blood, bone marrow or cutaneous lesions. In total, 109 cases of BPDCN were included in 35 hospitals (2000-2013). BPDCN is more prevalent in men (sex ratio 4.4/1) and in elderly subjects (median age: 63 years; 7 patients were Immunophenotype showed that HLA-DR and CD4 were expressed in all cases, but 4 cases did not express CD56 (confirmed using 3 different antibodies). Expression of markers of others hematopoietic lineages was frequent. Among myeloid markers, the most frequent was CD33 (46%), followed by CD117 (23%), whereas CD13, CD11c, CD15 and CD65 were rarely expressed. Monocyte markers (CD14, CD64, CD11b) and myeloperoxidase were never expressed. For the T lineage, CD2 and CD7 were the most frequent (62% and 58% respectively) whereas CD5 was rare (7%). No cytoplasmic or surface CD3 were detected. For the B lineage, CD22 was expressed in 16%, and low levels of cCD79a in 5%. Both were never expressed together, and no CD19, CD20 and immunoglobulins were found. Generally, we observed one of these antigens (Ags) per case, but in 44% of cases, there was a combination of 2 or 3 Ags from 2 or 3 different lineages. Immature Ags such as CD34 and CD133 were never found, and Tdt was found in 14% of cases. Cytogenetic analysis revealed abnormal caryotype in 65% of the 78 caryotypes evaluated, with 20 cases having a complex caryotype. The frequency of the chromosomal abnormalities involved are shown in Figure 1H. In conclusion, we describe the largest series of BPDCN to date in the literature. Detailed clinical and biological data at presentation allow improved recognition of this rare form of acute and aggressive leukemia, enabling early initiation of appropriate management. Figure 1. A: Blood cell count in 109 BPDCN patients at diagnosis. Bars represent the median. B: Typical BPDCN morphology. C: In this case, the nuclei were peripheral, cytoplasm presented heterogenous basophilia, vacuoles were rare but large pseudopodia are frequent. D: Typical morphology with frequent microvacuoles under the cytoplasmic membrane. E: Immature morphology. F: Pseudolymphocytic morphology. G: Presence of dysplasia in myeloid cells with Auer Rods in the granulocytes. The morphology of the Blastic cells is typical. H. Chromosomal abnormalities in 78 caryotypes evaluated: The histogram represents the number of cases in which each chromosome was involved (deletion, gain, translocations). Figure 1. A: Blood cell count in 109 BPDCN patients at diagnosis. Bars represent the median. B: Typical BPDCN morphology. C: In this case, the nuclei were peripheral, cytoplasm presented heterogenous basophilia, vacuoles were rare but large pseudopodia are frequent. D: Typical morphology with frequent microvacuoles under the cytoplasmic membrane. E: Immature morphology. F: Pseudolymphocytic morphology. G: Presence of dysplasia in myeloid cells with Auer Rods in the granulocytes. The morphology of the Blastic cells is typical. H. Chromosomal abnormalities in 78 caryotypes evaluated: The histogram represents the number of cases in which each chromosome was involved (deletion, gain, translocations). Disclosures Bardet: Celgene: Research Funding. Deconinck:CHUGAI: Other: Travel for international congress; PFIZER: Research Funding; ROCHE: Research Funding; NOVARTIS: Other: Travel for international congress; ALEXION: Other: Travel for international congress; JANSSEN: Other: Travel for international congress; LFB loboratory: Consultancy.

Published
2015

38. Transcriptional and post-transcriptional mechanisms induce cyclin-D1 over-expression in B-chronic lymphoproliferative disorders

Author

Jean Jacques Ballet, Brigitte Sola, Xavier Troussard, Véronique Salaun, Immunité de l'infection et transplantations, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Hématologie Biologique [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
Adult, Male, Transcriptional Activation, Cancer Research, Lymphoma, B-Cell, Transcription, Genetic, [SDV]Life Sciences [q-bio], Blotting, Western, Lymphoproliferative disorders, Chromosomal translocation, Biology, Gene product, Cyclin D1, hemic and lymphatic diseases, medicine, Humans, Aged, Aged, 80 and over, Regulation of gene expression, Leukemia, Hairy Cell, Reverse Transcriptase Polymerase Chain Reaction, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Molecular biology, 3. Good health, Lymphoma, Gene Expression Regulation, Neoplastic, Leukemia, Oncology, Karyotyping, Female, Lymphoma, Large B-Cell, Diffuse, Protein Processing, Post-Translational, Lymphoid leukemia
Abstract

International audience; Cyclin D1 participates in cell‐cycle control, in the progression through the G1 phase and in the transition from the G1 to the S phase. The CCND1 locus, located in 11q13, is amplified and cyclin‐D1 protein is over‐expressed in a wide range of human solid tumors. In some B‐lymphoid malignancies, the t(11;14)(q13;q32) translocation joins the Ig heavy‐chain locus to the CCND1 locus and leads to cyclin‐D1 over‐expression. In this study, a series of 127 patients presenting a B‐chronic lymphoproliferative disorder (B‐CLPD) was analyzed using a competitive RT‐PCR designed to detect cyclin‐D1‐mRNA over‐expression. Cyclin‐D1 mRNA was expressed in patients with mantle‐cell lymphoma (MCL; 10/10), hairy‐cell leukemia (HCL; 3/5), B‐chronic lymphoid leukemia (B‐CLL; 4/111) and B large‐cell lymphoma (BLCL; 1/1). Densitometric analysis of RT‐PCR products and Western‐blot autoradiograms, in addition to cytogenetic data, indicated that activation of the cyclin‐D1 gene occurred independently of the t(11;14)(q13;q32) translocation in patients with HCL. Indeed, a normal‐sized protein of 36 kDa exhibiting a level incompatible with gene activation by a translocation mechanism was detected in lymphoid cells with a normal karyotype. Moreover, we found a discrepancy between cyclin‐D1 mRNA and protein levels in MCL and B‐CLL, which suggested that some regulatory mechanisms acting at a post‐transcriptional level persist in tumor cells. Int. J. Cancer 83:230–234, 1999. © 1999 Wiley‐Liss, Inc.

Published
1999
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39. Biopsy-proven muscular involvement of lymphomatoid granulomatosis assessed by 18FDG-PET Scan

Author

Christophe Auzary, Hubert de Boysson, Loïk Geffray, Véronique Salaun, Alison Johnson, and Emmanuèle Lechapt-Zalcman

Subjects
medicine.medical_specialty, Lymphomatoid granulomatosis, medicine.diagnostic_test, business.industry, Joint bone, medicine.disease, Lymphoma, Rheumatology, Positron emission tomography, Biopsy, medicine, Radiology, Differential diagnosis, business
Abstract

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 24 janvier 2015

Published
2015
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40. Hematogones: an overview

Author

Sylvain Chantepie, Edouard Cornet, Véronique Salaun, and Oumedaly Reman

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Bone marrow transplantation, business.industry, Lymphoblast, Precursor Cells, B-Lymphoid, Hematology, Normal bone, medicine.anatomical_structure, Oncology, Hematologic Neoplasms, Immunology, Medicine, Animals, Humans, Bone marrow, business
Abstract

Hematogones were initially described as mysterious cells in bone marrow smears more than 70 years ago. These cells are normal bone marrow B-lymphocyte precursors with properties that overlap those of lymphoblasts. Their morphological and immunological features are described here with an update on the knowledge of hematogones in hematological and non-hematological disorders.

Published
2013

41. Biological markers and ovarian carcinomas: Galactosyltransferase, CA 125, isoenzymes of amylase and alkaline phosphatase

Author

J. P. Malas, Jacques Goussard, François Sichel, Edith Bara, Véronique Salaun, Pascal Gauduchon, and Jean-Yves Le Talaer

Subjects
Clinical Biochemistry, Population, Ovary, Sensitivity and Specificity, Biochemistry, Isozyme, Glycosaminoglycan galactosyltransferase, Ovarian carcinoma, Biomarkers, Tumor, medicine, Humans, Amylase, education, Ovarian Neoplasms, Galactosyltransferase, education.field_of_study, biology, Carcinoma, Liver Neoplasms, Biochemistry (medical), gamma-Glutamyltransferase, General Medicine, Alkaline Phosphatase, Galactosyltransferases, Prognosis, Isoenzymes, medicine.anatomical_structure, CA-125 Antigen, Amylases, biology.protein, Alkaline phosphatase, Female, Follow-Up Studies
Abstract

We present a comparative study of several biological markers (galactosyltransferase, CA 125, isoenzymes of amylase and alkaline phosphatase) with a view to ovarian carcinoma follow-up. Serum samples were obtained from a population of 75 patients under clinical observation. After a minimum 18-months period, we assessed the prognostic value of the markers. No marker permits the detection of discrete, evolving carcinomas. CA 125 is the marker that gives the best results, particularly in terms of sensitivity. Galactosyltransferase has a lower sensitivity except in the case of endometrioid carcinomas. Simultaneous analysis with CA 125 and galactosyltransferase results in no decisive improvement, other than greater precision in unfavourable prognoses. Isoenzymes of amylase and alkaline phosphatase are of no interest in the follow-up of such carcinomas.

Published
1994
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42. Hematogones: a new prognostic factor for acute myeloblastic leukemia

Author

Sylvain Chantepie, Jean-Jacques Parienti, Florence Truquet, Jean Pierre Vilque, Oumedaly Reman, Véronique Salaun, Margaret Macro, and Stéphane Cheze

Subjects
Oncology, medicine.medical_specialty, Acute myeloblastic leukemia, Immunology, Biochemistry, Disease-Free Survival, Recurrence, Internal medicine, medicine, Humans, Leukocytosis, Aged, Acute leukemia, Hematology, Hematologic Tests, business.industry, Precursor Cells, B-Lymphoid, Hazard ratio, Remission Induction, Myeloid leukemia, Cell Biology, Middle Aged, medicine.disease, Prognosis, Chemotherapy regimen, Survival Analysis, Confidence interval, Leukemia, Myeloid, Acute, medicine.symptom, business
Abstract

Acute myeloid leukemia (AML) patient outcomes remain heterogeneous, and new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B-lymphocyte precursors, which increase in number in hematologic diseases. The prognostic impact of the presence of detectable HGs on the leukemia-free survival (LFS) and overall survival of 120 consecutive patients with AML in first complete remission was investigated by flow cytometry. Patients who had HG levels more than 0.01% had a significantly better median LFS (29.2 vs 11.7 months; P = .001) and overall survival (not reached vs 23.5 months; P = .011). According to Cox analysis, an HG level more than 0.01% was an independent predictor of LFS (hazard ratio = 0.5; 95% confidence interval, 0.28-0.90, P < .03) when age, leukocytosis, the number of chemotherapy cycles, and the standardized cytogenetic and molecular risk subgroups were controlled for. These results indicate that HG analysis may help to define the risk of relapse in AML patients.

Published
2010

43. ZAP-70 intron1 DNA methylation status: Determination by pyrosequencing in B chronic lymphocytic leukemia

Author

Sophie Krieger, Christoph Grunau, Pascal Gauduchon, Dominique Vaur, Mélanie Briand, Mikel Roussel, Jean-Jacques Parienti, Stéphane Cheze, Natacha Heutte, Michel Leporrier, Sylvain Chantepie, Véronique Salaun, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Interactions Hôtes-Pathogènes-Environnements (IHPE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Perpignan Via Domitia (UPVD), Archéologie et Philologie d'Orient et d'Occident (AOROC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Groupe Régional d'Etudes sur le CANcer (GRECAN), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-IFR146, Unité de Biostatistique et de Recherche Clinique (UBRC), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre d’études des transformations des activités physiques et sportives (CETAPS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons (LDM-TEP), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie et écologie tropicale et méditerranéenne [2007-2010] (BETM), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Perpignan Via Domitia (UPVD), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-IFR146, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie moléculaire et cellulaire de la signalisation (BMCS), Normandie Université (NU)-Normandie Université (NU), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biologie et écologie tropicale et méditerranéenne (BETM), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-IFR146, Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Perpignan Via Domitia (UPVD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département des Sciences de l'Antiquité - ENS Paris (DSA ENS-PSL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT)

Subjects
Adult, Male, Cancer Research, ZAP-70, Chronic lymphocytic leukemia, [SDV]Life Sciences [q-bio], chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, medicine, Humans, Epigenetics, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, ZAP-70 Protein-Tyrosine Kinase, DNA methylation, medicine.diagnostic_test, Gene Expression Regulation, Leukemic, Pyrosequencing, hemic and immune systems, Sequence Analysis, DNA, Hematology, Methylation, Middle Aged, Flow Cytometry, Prognosis, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Molecular biology, Introns, Oncology, CpG site, 030220 oncology & carcinogenesis, Disease Progression, Female, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, IGHV@, CLL
Abstract

International audience; ZAP-70 expression is a strong prognostic indicator in chronic lymphocytic leukemia. However, ZAP-70 quantification by flow cytometry lacks sufficient standardization. Based upon the correlation between ZAP-70 expression and its gene methylation status, we have developed a quantitative pyrosequencing assay for the determination of ZAP-70 methylation adapted for routine use. Methylation in four CpG pairs (C-223, C-243, C-254, and C-267) in the first intron of ZAP-70 is associated with repression of ZAP-70. Moreover, it correlates with CD38 expression (n = 111, p < .0001), IgHv mutation status (n = 106, p < .0001), time to treatment (p < .0001), and overall survival (p = .0014). Pyrosequencing of ZAP-70 provides a good alternative to flow cytometry.

Published
2010
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45. Skin manifestations in CD4+, CD56+ malignancies

Author

Katell, Penven, Margaret, Macro, Véronique, Salaun, François, Comoz, Oumedaly, Reman, Dominique, Leroy, Xavier, Troussard, Tony, Petrella, and Anne, Dompmartin

Subjects
Aged, 80 and over, CD4-Positive T-Lymphocytes, Diagnosis, Differential, Male, Skin Neoplasms, Hematologic Neoplasms, Interleukin-3 Receptor alpha Subunit, Humans, Female, Middle Aged, CD56 Antigen, Receptors, Interleukin-3, Aged
Abstract

CD4+ CD56+ hematologic neoplasms were recently individualized. We report three cases of CD4+ CD56+ malignancies with cutaneous lesions in three cases and also bone marrow involvement in two cases. Two patients relapsed 2 and 3 months after polychemotherapy. Two patients died within 3-10 months. A constant immunophenotype was observed with the co-expression of CD4 and CD56, the absence of B and T-cell markers. The salient fact of this report is the presence of T-cell clonal rearrangement. The clinical and pathological features closely resemble the specific cutaneous manifestations in acute leukemia with monocytic differentiation, especially the granulocytic sarcoma. Because of the positivity of the CD56, natural killer cell proliferations were discussed. Since 1994, 50 cases of CD4+, CD56+ cutaneous neoplasms have been reported with specific clinical, cytologic and immunohistochemical features. The diagnosis is more difficult when the cutaneous location is exclusive; on the contrary, the cytological features of the blood and medullar cells with cytoplasmic vacuoles and pseudopodia are characteristic of this hematologic neoplasm. The presence of CD123 antigen in most of the cases is an argument for a plasmacytoid dendritic cell proliferation and it is also a good marker for primary cutaneous lesions.

Published
2003

46. 3.8 Epidemiology of CLL in Basse-Normandie (France)

Author

Albert Collignon, Virginie Duchenet, Xavier Troussard, Florence Truquet, Jean Marc-Poncet, Edouard Cornet, and Véronique Salaun

Subjects
Cancer Research, medicine.medical_specialty, Oncology, business.industry, Family medicine, Epidemiology, medicine, Hematology, business
Published
2011
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47. IgM multiple myeloma: More on a rare and heterogeneous disease

Author

Xavier Troussard, Sylvain Chantepie, Levaltier X, Quentin Cabrera, Véronique Salaun, and Margaret Macro

Subjects
biology, business.industry, Chromosomal translocation, Hematology, Disease, medicine.disease, Immunophenotyping, Text mining, Antigen, Immunoglobulin M, Immunology, biology.protein, medicine, business, Multiple myeloma
Published
2011
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48. Evaluation of the Interest of BRAF –V600E Mutation Detection By Arms-qPCR in Hairy Cell Leukemia Diagnosis and Treatment Monitoring

Author

Michèle Malet, Ouda Ghoual, Xavier Troussard, Stéphanie Jouve, Dina Istasi, Stéphane Cheze, and Véronique Salaun

Subjects
medicine.medical_specialty, Pathology, business.industry, Immunology, Myeloid leukemia, Cell Biology, Hematology, medicine.disease, Biochemistry, Gastroenterology, Minimal residual disease, Lymphoma, Leukemia, Internal medicine, medicine, Hairy cell leukemia, Mantle cell lymphoma, Rituximab, Prolymphocytic leukemia, business, medicine.drug
Abstract

Background: The discovery of BRAF V600E (Tiacci et al. N.Eng J Med, 2011), has introduced molecular biology in the management of Hairy cell leukemia (HCL). Various techniques for BRAF detection with a specificity of 100% were developed. According to literature, BRAF mutation has been reported in one case of CLL and one B-prolymphocytic leukemia (Langabeer et al. Leukemia research, 2012). The development of BRAF inhibitors for refractory HCL to purine nucleoside analogues (PNA) renders the detection of BRAF mutation indispensable for the diagnosis and monitoring of the minimal residual disease (MRD). Objectives: To test a quantitative PCR on HCL patients at diagnosis, during relapse and at MRD monitoring compared to flow cytometry (FCM), then evaluate its usage on peripheral blood (PB) versus bone marrow (BM) sampling. Methods: We developed a relative quantitative amplification refractory mutation PCR technique (ARMS-qPCR). A retrospective study on a total of 99 samples between 1998 and 2014 was conducted. These samples were previously analyzed by a 4 colors FCM. 38 patients with HCL were tested at diagnosis (21 samples from PB and 17 from BM). 36 patients with other hematologic malignancies were studied, 5 other hairy cell proliferations (3 HCL-Variant (HCL-V) and 2 splenic lymphocyte villous lymphomas SLVL) and 31 non hairy cell proliferations (13 chronic lymphocytic leukemias (CLL), 13 atypical CLL, 3 large B-cell non Hodgkin lymphomas, 2 mantle cell lymphomas, 1 marginal zone lymphoma, 1 acute myeloid leukemia, 1 mastocytosis). Subsequently, we studied 14 patients in relapse (8 samples from PB, 5 from BM and 1 from a diaphragm nodule). Among these patients, 9 had received PNA, 3 interferon (IFN), 1 PNA + rituximab and 1 patient with unknown treatment. We monitored 11 patients for MRD (6 samples from PB and 5 from BM), 6 were treated with PNA, 1 with IFN and 1 with PNA + rituximab and 3 patients with unknown treatment. Results: The sensitivity of our ARMS-qPcr technique attained 0.001%. At diagnosis, the tumor cells ranged from 0.5% to 91% in PB and 3% to 73% in BM. All patients diagnosed as HCL by FCM were also detected by our PCR technique. The average mutated BRAF allele was 8% (0.02-18%) at diagnosis in the PB and 6% (2.5 -14%) in BM. The mutation was not detected for any of the patients harboring other hairy cell proliferations. Of the 36 patients with other hematologic malignancies, no signal was detected except for a weak one for 2 CLL patients with atypical morphology and 1 mixed type CLL/prolymphocytic leukemia (mutated allele: 0.03%, 0.21% and 1% respectively). This tempers the total specificity of BRAF detection in HCL described in earlier publications. At relapse, tumor cells ranged from 0.3% to 81% in PB and 3% to 30% in BM. The average mutated BRAF allele was 5.4% (0.09% -20%) in PB and 3.4% (0.6% -7.5%) in BM. Concerning evaluation of MRD, tumor cells ranged from 0% to 3% in PB and 0% to 2% in BM. All patients having malignant cells detected by FCM were detected by ARMS-qPCR. 2 patients were undetectable by both methods, 1 was treated by PNA + rituximab and the treatment was unknown for the other. The average mutated BRAF allele was 0.5% (0% -1%) in PB and 0.3% (0% -1%) in BM. Patients treated by PNA or IFN and tested in our study were positive for the MRD. DNA was obtained simultaneously from PB and BM for 3 patients (2 diagnosis and 1 relapse). The BRAF mutated allele was similar in PB and BM for 2 patients (4% and 11% in PB, 4% and 14% in BM respectively) and the circulating tumor cells were 60% and 61%. As for the 3rd patient, a lower mutated allele percentage (0.09%) was detected with 1% of tumor cells in blood, where 4% of the mutated allele was found in BM with 25% of tumor cells. Conclusion: This ARMs-qPcr allowed the HCL diagnosis of 100% of tested patients and the differential diagnosis with other hairy cell proliferations though a weak signal was detected in 3 atypical CLL cases. Using this PCR for relapse detection and MRD monitoring is as performing as the FCM. PB sampling which is less invasive than BM puncture seems to be adequate for HCL molecular study. BM aspirate may be considered in case of diagnostic difficulties or very few tumor cells. All patients treated by PNA or IFN and tested in our study were positive for the MRD suggesting that a complete molecular response is hardly achieved with these drugs. This should be confirmed on a larger number of patients as well with the emerging therapies. Disclosures No relevant conflicts of interest to declare.

Published
2014
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49. Hematogones (medullar pro-B Cells) Are Present but Decreased in Active Multiple Myeloma and Are a Prognostic Factor in Treated Myeloma Patients

Author

Jean-Baptiste Mear, Edouard Cornet, Xavier Troussard, Véronique Salaun, Quentin Cabrera, Sylvain Chantepie, Oumedaly Reman, and Margaret Macro

Subjects
medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Immunology, CD34, Cell Biology, Hematology, Hematopoietic stem cell transplantation, medicine.disease, Biochemistry, Gastroenterology, medicine.anatomical_structure, Internal medicine, medicine, Progression-free survival, Bone marrow, Hypoalbuminemia, business, Multiple myeloma, Monoclonal gammopathy of undetermined significance
Abstract

BACKGROUND Hematogones (HG) are normal bone marrow B-cells precursors, characterized on Multiparameter Flow Cytometry (MFC) study by CD19 expression, progressive loss of CD10 and CD34, acquisition of CD45 and CD20. HG level is lowered by age or medullar tumoral infiltration, but is higher (>5%) after chemotherapy, Hematopoietic Stem Cell Transplantation (HSCT) or viral infection. An HG level >0.01% in first complete remission in Acute Myeloid Leukemia (AML) patients is associated with a better Overall Survival (OS) and Progression Free Survival (PFS). Further correlations have been made between HG level and good evolutions in AML patients or HSCT recipients. Although Multiple Myeloma (MM) is a mature B-cell malignancy, no clinical study has focused on HG in MM patients. Furthermore, there is no data on prognostic impact of HG in treated MM patients. However, HG study could be of prime interest for medullar micro-environment evaluation which is not assessed by routine prognostic factors. AIM Our primary objective was to establish the presence and level of HG in the bone marrow of patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), Smoldering Myeloma (SM) or active MM (aMM), and to analyze correlations with clinical characteristics. Our secondary objective was to determine a prognostic correlation between HG level at diagnosis and PFS or OS in aMM patients. METHODS In this monocentric prospective observational study conducted between March 2011 and January 2014, we analyzed all bone marrow samples sent to the MFC lab in our center of CHU de Caen, France. Samples were routinely obtained by bone marrow aspirations at diagnosis for MGUS or MM patients. Medullar cells were analyzed by 4-color MFC, using a CD20-FITc/CD19-PE/CD45-PerCp/CD10-APC panel for HG detection. HG level was calculated over all nuclear medullar cells, samples with less than 100.000 cells were excluded, and sensitivity was 1/104 cells. All biological data were recorded at diagnosis. The median follow-up was 16 months. All statistical analysis, including multivariate analysis, were performed with two-sided 95% confidence intervals. RESULTS A total of 90 patients have been included: 25 MGUS (27%), 12 SM (13%) and 53 aMM (58%). The mean age at diagnosis was respectively 63, 68 and 67 y (35-90), and mean β2-µglobulinemia (β2) was 2.5, 5 and 6.3 mg/l respectively. HG were detected in more than 90% of cases. The mean HG level was significantly higher in MGUS (2.86%, median 2%, p=0.006) or in SM (1.95%, median 1.5%, p=0.019) than in aMM (1.10% median 0.5%) (Figure 1). HG level at diagnosis was inversely correlated with age, plasma cell infiltration, hypoalbuminemia, or β2 (mean HG=2% if β2≤3.5 mg/l, and 0.8% if β2>5 mg/l). HG level was higher in patients with hemoglobin levels ≥10 g/dL (2.8% vs 0.7%, p=0.015). There were no correlations between HG level at diagnosis and white blood cells count, gender, renal insufficiency, plasma cell phenotype nor monoclonal component subtype. In the subgroup of 53 aMM patients, 22% were ISS1, 29% were ISS2 and 49% ISS3. Mean HG levels were 2.1%, 0.8% and 0.85% respectively (p=0.008 between ISS1 vs ISS2+3). All patients but one received a triple regimen chemotherapy including Bortezomib. Patients with HG level >0.5% at diagnosis (median of the group) had a longer median PFS (29.8 vs 13.5 months, n=26 and 27, p=0.002, cf. Figure 2) and a better OS (85% alive vs 60% at 20 months, median not reached, p=0.02). In multivariate analysis, a cut-off of 0.5% of HG at diagnosis was a prognostic factor for PFS in aMM patients (p=0.03, IC=0.14-0.9), with age (p=0.041, IC=1.0-1.09) but not ISS subgroup (p=0.6). Furthermore, patients who achieved Very Good Partial Response (VGPR) or more had higher HG level at diagnosis than patients who achieved Partial Response or less (IC=1.08-6.07, p=0.015). CONCLUSION HG are present in MM patients. The HG level is decreased in MM patients as compared to MGUS, and is inversely correlated with the disease biomarkers or activity. An HG level >0.5% at diagnosis is a good prognostic factor in treated MM patients, and may reflect bone marrow micro-environment condition. Figure 1. HG level and disease stage at diagnosis. Figure 1. HG level and disease stage at diagnosis. Figure 2. PFS of aMM patients sort by HG at diagnosis. Figure 2. PFS of aMM patients sort by HG at diagnosis. Disclosures No relevant conflicts of interest to declare.

Published
2014
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50. Pratique de la cytométrie en flux sur peau dans les lymphomes cutanés T épidermotropes et érythrodermiques : un outil diagnostique ?

Author

R. Morello, A. Tesnière, F. Comoz, Véronique Salaun, L. Verneuil, and S. Lecot

Subjects
Dermatology
Abstract

Introduction Les lymphomes cutanes T erythrodermiques (LCTE) (syndromes de Sezary [SS] et mycosis fongoides erythrodermiques [MFE]) representent environ 5 % des erythrodermies. Leur diagnostic est souvent difficile et necessite une confrontation des donnees cliniques, histologiques, immuno-histochimiques et de biologie moleculaire. Peu de donnees sont disponibles concernant l’interet de l’immunophenotypage lymphocytaire cutane dans les lymphomes cutanes T, principalement etudie dans les lymphomes B. Patients et methodes Entre aout 2004 et juillet 2013, les dossiers de patients presentant un lymphome T epidermotrope (SS, MF erythrodermique [MFE] et MF) ayant eu un immunophenotypage cutane au diagnostic etaient analyses. Ces donnees etaient comparees a un groupe de temoins erythrodermiques (TE) presentant une dermatose inflammatoire. Resultats Quarante-cinq patients ont ete inclus : 33 lymphomes cutanes T (LCT) dont 13 SS, 6 MFE, 14 MF et 12 TE (5 eczemas, 3 psoriasis, 1 DRESS, 1 purpura rhumatoide, 1 photoallergie et 1 erythrodermie idiopathique). La cytometrie en flux sur peau etait contributive pour les 13 SS, 6 MFE et 11 MF (Se = 100 %, Spe = 75 %), contre 3 TE ( p p = 0,07 ; MFE : sensibilite = 17 %, specificite = 92 %, p = 1). Dans le groupe SS, la cytometrie sur peau permettait la detection de la perte d’expression du CD7 dans 12 cas contre 4 par immuno-histochimie ( p = 0,04). La comparaison de la cytometrie sur sang et peau ne montrait une difference que pour le groupe MF ( p = 0,002). Dans ce groupe, la cytometrie etait contributive dans 3 cas/4 ou l’histologie ne permettait pas de retenir le diagnostic. Discussion Nos resultats montrent une bonne valeur predictive positive (81 %) et une valeur predictive negative (100 %) de la cytometrie en flux sur peau pour le diagnostic des SS/MFE compare aux erythrodermies non lymphomateuses en cas d’histologie non specifique. Dans le contexte de Sezary, la cytometrie cutanee etait plus sensible mais moins specifique pour la detection de la perte d’expression du CD7 comparee a l’IHC (se : 92 % vs 36 % ; spe : 75 % vs 100 %) ; elle reste a evaluer pour le marqueur CD26. Neanmoins, ces resultats obtenus par cytometrie sur peau n’etaient pas superieurs a ceux obtenus dans le sang. Pour les MF, la cytometrie en flux etait positive meme en cas d’histologie non contributive, ce qui n’etait pas retrouve auparavant dans les deux series publiees. Conclusion La cytometrie en flux pratiquee sur peau a une grande valeur diagnostique pour les erythrodermies lymphomateuses et permet de les differencier des dermatoses inflammatoires, contrairement a l’histologie. De plus, elle apparait interessante pour les MF, en complement de l’histologie ou en cas d’histologie non contributive.

Published
2014
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