Search

Your search keyword '"Service d'Hématologie Biologique [CHU Nantes]"' showing total 11 results
Start Over Author "Service d'Hématologie Biologique [CHU Nantes]" Topic [sdv.can] life sciences [q-bio]/cancer
11 results on '"Service d'Hématologie Biologique [CHU Nantes]"'

1. ALL relapse after anti-CD19 CAR-T cells therapy in a young adult: which therapeutic options?

Author

Grain, Audrey, Ollier, Jocelyn, Guillaume, Thierry, Chevallier, Patrice, Le Calvez, Baptiste, Eveillard, Marion, Clémenceau, Béatrice, Ollier, Jocelyn, Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service d'Hématologie et Oncologie pédiatriques [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Hématologie [CHU Nantes], and Service d'Hématologie Biologique [CHU Nantes]

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract

International audience; T-cells expressing a Chimeric Antigen Receptor (CAR) recognizing the CD19 antigen allowed high early response rates in high-risk B acute lymphoblastic leukemias (B-ALL). Nevertheless, 35% to 44% of patients relapse. Among the mechanisms of immune evasion in CD19+ relapses of ALL, expression and secretion of molecules inhibiting cytotoxic T-lymphocytes, or lack of expression of co-stimulatory molecules, have been described. Expansion, persistence and cytotoxic activity of CAR-T cells could also be deficient.Here, we present the case of a young adult who presented successive relapses of ALL after chemotherapy, hematopoietic stem cell transplant (HSCT) and anti-CD19 CAR-T cells. An extended immunophenotype of leukemic cells and sensitivity to anti-CD19 CAR-T cells mediated lysis are analysed.

Published
2022

2. Impact of KIR/HLA Incompatibilities on NK Cell Reconstitution and Clinical Outcome after T Cell–Replete Haploidentical Hematopoietic Stem Cell Transplantation with Posttransplant Cyclophosphamide

Author

Dhon Roméo Makanga, Catherine Willem, Marie C. Béné, Alice Garnier, Thierry Guillaume, Katia Gagne, Anne Cesbron, Nolwenn Legrand, Christelle Retière, Bercelin Maniangou, Amandine Le Bourgeois, Patrice Chevallier, Pierre Peterlin, Bernardo, Elizabeth, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Etablissement Français du Sang [Nantes], LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Service d'Hématologie Biologique [CHU Nantes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), and LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes]

Subjects
Adult, Male, Cyclophosphamide, medicine.medical_treatment, Immunology, Cell, Graft vs Leukemia Effect, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Human leukocyte antigen, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, [SDV.CAN] Life Sciences [q-bio]/Cancer, HLA Antigens, medicine, Humans, Immunology and Allergy, Receptor, Aged, business.industry, Donor selection, Hematopoietic Stem Cell Transplantation, Middle Aged, 3. Good health, Killer Cells, Natural, Transplantation, Treatment Outcome, medicine.anatomical_structure, Blood Group Incompatibility, Transplantation, Haploidentical, Female, business, Immunosuppressive Agents, 030215 immunology, medicine.drug
Abstract

P.C. and C.R. have equally contributed to this work; International audience; Little is known regarding the effect of KIR/HLA incompatibilities (inc.) in the setting of T-replete haploidentical allogeneic he-matopoietic stem cell transplantation using posttransplant cyclophosphamide (PTCy). In this retrospective study, the impact of KIR/HLA inc. on clinical outcomes and NK cell reconstitution was studied in a cohort of 51 consecutive patients receiving a T cell-replete haploidentical allogeneic hematopoietic stem cell transplantation after a reduced-intensity conditioning using peripheral blood stem cells as the source of the graft and PTCy as graft-versus-host disease (GvHD) prophylaxis. The NK cell repertoire reconstitution was examined by multiparameter flow cytometry in 34 of these 51 patients from day 0 to day 100 post-transplant. Genetic KIR2DL/HLA inc. were found to be significantly associated with more GvHD (81.2 versus 45.7%, p = 0.01) and less relapse (6.2 versus 42.8%, p = 0.008) in this context. GvHD is associated with increased levels of differentiated and activated NK cells. A significant loss of KIR2DL2/3 + NK cells was observed at day 30 in patients with inhibitory KIR/HLA inc., suggesting that responsive KIR NK cells are particularly targeted by the immunosuppressive PTCy treatment. Further investigations are needed from a larger cohort with an identical clinical approach to consolidate these results and to identify the NK cell subsets that may be beneficial for the graft-versus-leukemia effect observed. Because many haploidentical donors can be identified in a family, the prediction of KIR NK cell alloreactivity could be of crucial importance for donor selection and patient outcome.

Published
2019
Full Text
View/download PDF

3. A phase I/II feasibility vaccine study by autologous leukemic apoptotic corpse-pulsed dendritic cells for elderly AML patients

Author

Patrice Chevallier, Nadine Juge-Morineau, Thierry Guillaume, Céline Bossard, Marie C. Béné, Pierre Peterlin, Virginie Dehame, Brigitte Dréno, Isabelle Gauvrit, Yannick Le Bris, Marc Grégoire, Soraya Saiagh, Sylvain Bercegeay, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de Thérapie Cellulaire et Génique [CHU Nantes] (UTCG), Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Service d'Hématologie Biologique [CHU Nantes], Laboratoire d'anatomie et cytologie pathologiques [CHU Nantes], Etablissement Français du Sang [Pays de la Loire] (EFS Pays de la Loire), EFS, Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Bernardo, Elizabeth, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
030231 tropical medicine, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cancer Vaccines, Dendritic cells, 03 medical and health sciences, 0302 clinical medicine, AML, [SDV.CAN] Life Sciences [q-bio]/Cancer, vaccine, Cadaver, Immunology and Allergy, Medicine, Humans, 030212 general & internal medicine, Adverse effect, Aged, Pharmacology, business.industry, Complete remission, Myeloid leukemia, apoptotic corpses, 3. Good health, Leukemia, Myeloid, Acute, Phase i ii, Apoptosis, Cancer research, Feasibility Studies, business, Research Paper
Abstract

This was a phase I/II study testing the feasibility of a vaccine by autologous leukemic apoptotic corpse-pulsed dendritic cells (DC) in elderly acute myeloid leukemia (AML) patients in first or second complete remission. Pulsed DC were administered at doses of 9 × 10(6) subcutaneously (1 mL) and 1 × 10(6) intra-dermally (0.1 mL). Five doses of vaccine were planned on days +1 + 7 + 14 + 21 and +35. Five DC-vaccines were produced and injected for all five patients included in the study. No severe adverse event was documented. Larger Phase 2 studies are now required to precise the role of DC-vaccines with leukemic apoptotic bodies in older as well as younger AML populations. (Clinicaltrials.gov NCT01146262)

Published
2021
Full Text
View/download PDF

4. Diagnosis and prognosis are comforted by integrated assessment of next-generation sequencing in chronic myeloid malignancies. A real-life study

Author

Olivier Theisen, Pierre Peterlin, Viviane Dubruille, Patrice Chevallier, Pascal Godmer, Amandine Le Bourgeois, Sylvain Thepot, Anne Parcelier, Marion Loirat, Steven Le Gouill, Adrien Trebouet, Damien Luque Paz, Mélanie Mercier, S. Vigouroux, Mathilde Hunault, Céline Bossard, Marie C. Béné, Marion Eveillard, Audrey Ménard, Alice Garnier, Nadine Morineau, Camille Debord, Hervé Maisonneuve, François Subiger, Catherine Godon, Yannick Le Bris, Elsa Lestang, Jacques Delaunay, Sophie Vantyghem, Soraya Wuilleme, Anne Moreau, Ronan Le Calloch, Philippe Moreau, Lenaïg Le Clech, Thierry Guillaume, Bruno Villemagne, Valérie Ugo, Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département d'Hématologie Clinique [CHU d'Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Hématologie Biologique [CHU Nantes], Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Hôpital privé du Confluent [Nantes], Hématologie clinique [CH La Roche-sur-Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Laboratoire de Biologie [CHD Vendée, La Roche sur Yon], CHD Vendee (La Roche Sur Yon), Centre hospitalier de Saint-Nazaire, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Laboratoire d'Hématologie Biologique (Hémato - ANGERS), Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), Département de Pathologie [CHU Nantes], Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), and Bernardo, Elizabeth

Subjects
Oncology, medicine.medical_specialty, Myeloid, Somatic cell, diagnosis, theranostic, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Group B, DNA sequencing, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Neoplasms, medicine, Humans, 030304 developmental biology, 0303 health sciences, Myeloproliferative Disorders, business.industry, Myelodysplastic syndromes, Editorials, High-Throughput Nucleotide Sequencing, Hematology, Chronic Myeloproliferative Disorders, medicine.disease, Prognosis, somatic mutation by NGS, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Mutation, Bone marrow, business
Abstract

Next-generation sequencing (NGS) is used to investigate the presence of somatic mutations. The utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains unclear. We report the findings of an observational, multicenter study that aimed to assess the impact of somatic mutation testing by NGS in a reallife setting of chronic myeloid malignancies. A total of 177 patients were enrolled, partitioned into two overlapping groups. In group A (n=94), the indication was to search for clonal hematopoiesis, in a context of suspected myelodysplastic syndrome or myeloproliferative neoplasia. In group B (n=95), the theranostic impact of somatic mutations was studied. A panel of 34 genes was used on DNA extracted from blood or bone marrow samples. Within group A, the detection of clonal hematopoiesis supported the diagnosis of chronic myeloid malignancies for 31 patients while the absence of clonal hematopoiesis ruled out the suspected diagnosis in 47 patients. Within group B, NGS identified prognostically relevant somatic mutations in 32 patients, which had a therapeutic impact in 18 cases. By determining the presence or absence of somatic mutations, the application of NGS in daily practice was found to be useful for an integrated final diagnosis in 83% of the patients. Moreover, the search for somatic mutations had a prognostic impact that led to treatment modification in 19% of the cases. This study outlines the fact that adequate implementation of new investigations may have a significant positive medico-economic impact by enabling appropriate management of patients.

Published
2021
Full Text
View/download PDF

5. Centromeric KIR AA Individuals Harbor Particular KIR Alleles Conferring Beneficial NK Cell Features with Implications in Haplo-Identical Hematopoietic Stem Cell Transplantation

Author

Dubreuil, Léa, Maniangou, Bercelin, Chevallier, Patrice, Quéméner, Agnès, Legrand, Nolwenn, Béné, Marie C., Willem, Catherine, David, Gaëlle, Alizadeh, Mehdi, Makanga, Dhon Roméo, Cesbron, Anne, Gendzekhadze, Ketevan, Gagne, Katia, Retière, Christelle, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Etablissement Français du Sang [Nantes], LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Biologique [CHU Nantes], Etablissement français du sang [Rennes] (EFS Bretagne), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), City of Hope Medical Center [Duarte, CA, USA] (HLA laboratory), Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)

Subjects
HLA, haplo-identical HSCT, [SDV.CAN] Life Sciences [q-bio]/Cancer, leukemia, [SDV.CAN]Life Sciences [q-bio]/Cancer, NK cells, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article, KIR, polymorphism
Abstract

Simple Summary We have recently shown a broad disparity of Natural Killer (NK) cell responses against leukemia, highlighting good and bad responders resting on the Killer cell Immunoglobulin-like Receptors (KIR) and HLA genetics. In this study, we deeply investigated KIR2DL NK cell repertoire in combining high-resolution KIR allele typing and multicolor flow cytometry from a cohort of 108 blood donors. Our data suggest that centromeric (cen) AA individuals display more efficient KIR2DL alleles (L1*003 and L3*001) to mount a consistent frequency of KIR2DL+ NK cells and to confer an effective NK cell responsiveness. The transposition of our in vitro observations in T-replete haplo-identical Hematopoietic Stem Cell Transplantation (HSCT) context led us to observe that cenAA HSC grafts limit significantly the incidence of relapse in patients with myeloid diseases after T-replete haplo-identical HSCT. As NK cells are crucial in HSCT reconstitution, one could expect that the consideration of KIR2DL1/2/3 allelic polymorphism could help to refine scores used for HSC donor selection. Abstract We have recently shown a broad disparity of Natural Killer (NK) cell responses against leukemia highlighting good and bad responders resting on the Killer cell Immunoglobulin-like Receptors (KIR) and HLA genetics. In this study, we deeply studied KIR2D allele expression, HLA-C recognition and functional effect on NK cells in 108 blood donors in combining high-resolution KIR allele typing and multicolor flow cytometry. The KIR2DL1*003 allotype is associated with centromeric (cen) AA motif and confers the highest NK cell frequency, expression level and strength of KIR/HLA-C interactions compared to the KIR2DL1*002 and KIR2DL1*004 allotypes respectively associated with cenAB and BB motifs. KIR2DL2*001 and *003 allotypes negatively affect the frequency of KIR2DL1+ and KIR2DL3+ NK cells. Altogether, our data suggest that cenAA individuals display more efficient KIR2DL alleles (L1*003 and L3*001) to mount a consistent frequency of KIR2DL+ NK cells and to confer an effective NK cell responsiveness. The transposition of our in vitro observations in the T-replete haplo-identical HSCT context led us to observe that cenAA HSC grafts limit significantly the incidence of relapse in patients with myeloid diseases after T-replete haplo-identical HSCT. As NK cells are crucial in HSCT reconstitution, one could expect that the consideration of KIR2DL1/2/3 allelic polymorphism could help to refine scores used for HSC donor selection.

Published
2020
Full Text
View/download PDF

6. Whole genome copy number analysis in search of new prognostic biomarkers in first line treatment of mantle cell lymphoma. A study by the LYSA group

Author

Stephane Minvielle, Danielle Canioni, Florence Magrangeas, Marie-Hélène Delfau-Larue, Marie-Christine Béné, Olivier Pichon, Benoit Tessoulin, Hervé Maisonneuve, Catherine Guérin-Charbonnel, Olivier Hermine, Emmanuel Gyan, Yannick Le Bris, Catherine Pellat-Deceunynck, Olivier Theisen, Anne Moreau, David Chiron, Lucie Oberic, Barbara Burroni, Catherine Thieblemont, Steven Le Gouill, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Département de Pathologie [CHU Nantes], Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service de Pathologie [AP-HP Hôpital Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie clinique [CH La Roche-sur-Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d’Hématologie Clinique [CHU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Necker - Enfants Malades [AP-HP], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth

Subjects
Oncology, Male, Cancer Research, Copy number anomalies, Lymphoma, Mantle-Cell, Translocation, Genetic, Loss of heterozygosity, 0302 clinical medicine, International Prognostic Index, CDKN2A, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Cyclin D1, Prospective Studies, Univariate analysis, Hematology, General Medicine, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, Survival Rate, prognosis, 030220 oncology & carcinogenesis, Cohort, Female, Adult, medicine.medical_specialty, DNA Copy Number Variations, Copy number analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, CCND1/IGH, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, neoplasms, Cyclin-Dependent Kinase Inhibitor p16, Aged, Mantle cell lymphoma, Whole Genome Sequencing, business.industry, Genome, Human, medicine.disease, Lymphoma, Neoplasm Recurrence, Local, Tumor Suppressor Protein p53, business, 030215 immunology, Follow-Up Studies, Stem Cell Transplantation
Abstract

International audience; Mantle cell lymphoma (MCL) is a lymphoproliferative disorder characterized by the t(11;14)(q13;q32) CCND1/IGH translocation. This lymphoma is however extremely heterogeneous in terms of molecular alterations. Moreover, the course of the disease can vary greatly between indolent forms with slow progression and aggressive conditions rapidly pejorative. The identification of early markers allowing to predict individual patients outcome has however been unsuccessful so far. The LyMa trial treated homogeneously a cohort of young MCL patients. This appeared as a good opportunity to search for biomarkers of response to therapy. DNA extracted from diagnostic paraffin-embedded lymph node biopsies from 100 patients with newly diagnosed MCL, homogeneously treated in this prospective clinical trial, were investigated for copy number alterations and copy neutral loss of heterozygosity using the Oncoscan® SNP-array scanning the whole genome. An independent confirmatory cohort was used to strengthen the possibly relevant anomalies observed. Here we describe the recurrent anomalies identified with this technique. Deletions of 17p(TP53) and 9p(CDKN2A) were more frequent in refractory or early relapsing patients (10%), but had no significant impact in univariate analysis on progression-free (PFS) or overall survival (OS). Regardless of the presence of TP53 or CDKN2A deletions, gains in 7p22 (8,5%) were associated with better PFS in univariate but not in multivariate analysis including MCL International Prognostic Index and treatment. Gains of 11q(CCDN1), suggesting gains of the CCND1/IGH fusion, were associated with worse OS and PFS in univariate and multivariate analyses. This worse prognosis impact was confirmed by FISH in an independent confirmatory cohort. This work, using a whole genome approach, confirms the broad genomic landscape of MCL and shows that gains of the CCND1/IGH fusion can be considered as a new prognostic structural variant. Genomic abnormalities of prognostic impact could be useful to strengthen or de-escalate treatment schedules or choosing targeted therapies or CART-cells. This article is protected by copyright. All rights reserved.

Published
2020
Full Text
View/download PDF

7. Comparison of MALDI‐TOF mass spectrometry analysis of peripheral blood and bone marrow‐based flow cytometry for tracking measurable residual disease in patients with multiple myeloma

Author

Amanda Ciardiello, Even H Rustad, Yanming Zhang, Mikhail Roshal, Marion Eveillard, Neha Korde, Sydney X. Lu, Alexander M. Lesokhin, Sham Mailankody, Malin Hultcrantz, Ola Landgren, Katie L. Thoren, Urvi A Shah, Hani Hassoun, Eric L. Smith, Bernardo, Elizabeth, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Memorial Sloane Kettering Cancer Center [New York], Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Myeloma Service [New York, NY, USA] (Department of Medicine), Department of Pathology [New-York, NY, USA], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Neoplasm, Residual, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass spectrometry, Article, Flow cytometry, 03 medical and health sciences, Immunoglobulin kappa-Chains, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Recurrence, medicine, Humans, In patient, Multiple myeloma, Aged, mass spectrometry, medicine.diagnostic_test, business.industry, flow cytometry, Cancer, Bone Marrow Examination, Hematology, Middle Aged, medicine.disease, Peripheral blood, 3. Good health, multiple myeloma, medicine.anatomical_structure, Myeloma Proteins, 030220 oncology & carcinogenesis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Monoclonal, Female, Bone marrow, business, 030215 immunology
Abstract

International audience; Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) may soon replace routine electrophoretic methods for monitoring monoclonal proteins in patients with multiple myeloma. To further evaluate the clinical utility of this assay, we compared the performance of MALDI-TOF-MS head-to-head with an established bone marrow-based measurable residual disease assay by flow cytometry (Flow-BM-MRD), using Memorial Sloan Kettering Cancer Center's 10-color, single-tube method. Our results suggest that MALDI-TOF-MS adds value to bone marrow-based MRD testing and may be most useful for early detection of relapse in peripheral blood compared to current electrophoretic methods.

Published
2020
Full Text
View/download PDF

8. CSF1R and BTK inhibitions as novel strategies to disrupt the dialogue between mantle cell lymphoma and macrophages

Author

Papin, Antonin, Tessoulin, Benoit, Bellanger, Céline, Moreau, Anne, Le Bris, Yannick, Maisonneuve, Hervé, Moreau, Philippe, Touzeau, Cyrille, Amiot, Martine, Pellat-Deceunynck, Catherine, Le Gouill, Steven, Chiron, David, Bernardo, Elizabeth, NExT (I-SITE) - - NExT (I-SITE)2016 - ANR-16-IDEX-0007 - IDEX - VALID, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Microenvironnement des niches tumorales [UNIV Tours] (CNRS GDR 3697 MicroNiT), Université de Tours-Centre National de la Recherche Scientifique (CNRS), L’Héma-NexT [UNIV Nantes] (i-Site NexT), Université de Nantes (UN), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie Pathologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre Hospitalier Universitaire G. R. Laennec (HGRL Saint-Herblain), Service d'Hématologie Biologique [CHU Nantes], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), This study was supported by la Ligue Contre le Cancer Grand-Ouest, i-Site NexT (ANR-16-IDEX-0007) and the SIRIC ILIAD (INCa-DGOS-Inserm_12558). We thank Janssen-Cilag and Roche for supporting in part this study., ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée)

Subjects
Lymphoma, CD163+ macrophages, [SDV.CAN] Life Sciences [q-bio]/Cancer, immune system diseases, ibrutinib, hemic and lymphatic diseases, CSF1, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; The microenvironment strongly influences mantle cell lymphoma (MCL) survival, proliferation and chemoresistance. However, little is known regarding the molecular characterization of lymphoma niches. Here, we focused on the interplay between MCL cells and associated monocytes/macrophages. Using circulating MCL cells (n=58), we showed that, through the secretion of CSF1 and, to a lesser extent, IL-10, MCL polarized monocytes into specific CD163+ M2-like macrophages (MϕMCL). In turn, MϕMCL favored lymphoma survival and proliferation ex vivo. We next demonstrated that BTK inhibition abrogated CSF1 and IL-10 production in MCL cells leading to the inhibition of macrophage polarization and consequently resulting in the suppression of microenvironment-dependent MCL expansion. In vivo, we showed that CSF1 and IL-10 plasma concentrations were higher in MCL patients than in healthy donors, and that monocytes from MCL patients overexpressed CD163. Further analyses of serial samples from ibrutinib-treated patients (n=8) highlighted a rapid decrease of CSF1, IL-10 and CD163 in responsive patients. Finally, we showed that targeting the CSF1R abrogated MϕMCL-dependent MCL survival, irrespective of their sensitivity to ibrutinib. These data reinforced the role of the microenvironment in lymphoma and suggested that macrophages are a potential target for developing novel therapeutic strategies in MCL.

Published
2019

9. FLT3 ligand plasma levels in acute myeloid leukemia

Author

Nelly Robillard, Alice Garnier, Soraya Wuilleme, Marion Eveillard, Olivier Theisen, Patrice Chevallier, Michel Chérel, Yannick Le Bris, Thierry Guillaume, Nicolas Blin, Steven Le Gouill, Camille Debord, Beatrice Mahe, Philippe Moreau, Pierre Peterlin, Amandine Le Bourgeois, Viviane Dubruille, Catherine Godon, Anne Lok, Joëlle Gaschet, Thomas Gastinne, Antoine Bonnet, Marie-Christine Béné, Cyrille Touzeau, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service d'Hématologie Biologique [CHU Nantes], Unité de Médecine Nucléaire [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), This study was supported by a grant from the DHU Oncogreffe of Nantes., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
Acute Myeloid Leukemia, Myeloid, Time Factors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Online Only Articles, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Proportional Hazards Models, 0303 health sciences, business.industry, Myeloid leukemia, Disease Management, Membrane Proteins, Hematology, Plasma levels, Induction Chemotherapy, medicine.disease, Prognosis, cytokines, Leukemia, Leukemia, Myeloid, Acute, Adult Acute Lymphoblastic Leukemia, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, Flt3 ligand, business, Biomarkers
Abstract

International audience; no abstract

Published
2019
Full Text
View/download PDF

10. Two novel variants of uncertain significance in GP9 associated with Bernard–Soulier syndrome: Are they true mutations?

Author

G. Landeau, Marc Fouassier, S. Bezieau, Marie C. Béné, Camille Debord, Pierre Boisseau, C. Thomas, B. Pan Petesch, M. Giraud, M. Sigaud, Marion Eveillard, Agnès Quéméner, P. Talarmain, Service de génétique médicale [CHU Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'Hématologie Biologique [CHU Nantes], Immunobiology of Human αβ and γδ T cells and Immunotherapeutic Applications ( CRCINA - Département INCIT - Equipe 1 ), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Régional de Traitement des Hémophiles [CHU Nantes], Centre Régional de Traitement des Hémophiles [CHU Brest], Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth

Subjects
0301 basic medicine, Models, Molecular, Genotype, Protein Conformation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bernard–Soulier syndrome, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Structure-Activity Relationship, 0302 clinical medicine, Von Willebrand factor, [SDV.CAN] Life Sciences [q-bio]/Cancer, Glycoprotein complex, Thrombocytopathy, medicine, Humans, Platelet, Alleles, Genetic Association Studies, chemistry.chemical_classification, biology, GP9, Bernard-Soulier Syndrome, Computational Biology, Genetic Variation, Hematology, General Medicine, Sequence Analysis, DNA, medicine.disease, 3. Good health, 030104 developmental biology, Phenotype, chemistry, Platelet Glycoprotein GPIb-IX Complex, Child, Preschool, Immunology, Mutation, biology.protein, Anisocytosis, Female, Glycoprotein, Biomarkers, 030215 immunology, Rare disease
Abstract

International audience; Bernard–Soulier syndrome (BSS) is an autosomal recessive major thrombocytopathy, the symptoms of which are mainly marked by mucocutaneous bleeding. This rare disease, initially described in the 1970s, is the result of an abnormal formation of the glycoprotein complex Ib-IX-V (GP Ib-IX-V), a platelet receptor of von Willebrand factor. A large number of mutations, sometimes involving the GP9 gene, have been described as possibly responsible for the disease. We report here the case of a BSS patient who presented with persistent thrombocytopenia (31x10[9]/L) and decreased surface expression of GPIb-IX-V on large platelets with anisocytosis. Thorough molecular analyses disclosed two previously unreported GP9 variants, respectively c.230T>A (p.Leu77Gln) and c.255C>A (p.Asn85Lys). Both are likely to modify the conformation of GP-IX interactions with other glycoproteins of the Ib-IX-V complex and thus proper expression of this complex on the membrane of platelets.

Published
2017
Full Text
View/download PDF

11. Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial

Author

Didier Bouscary, E. Tavernier, Mathilde Hunault-Berger, A Saad, Chantal Himberlin, Severine Lissandre, Christian Recher, Isabelle Luquet, F Orsini-Piocelle, M-A Couturier, Etienne Daguindau, N. Maillard, M C Béné, Caroline Bonmati, Francois Dreyfus, Martin Carre, J-P Marolleau, A Schmidt-Tanguy, Jacques Delaunay, Norbert Ifrah, Luc Fornecker, Mario Ojeda-Uribe, M Puyade, B. Choufi, J-F Hamel, Arnaud Pigneux, Marc Bernard, Anne Banos, L Sutton, V Rouillé, Laurence Sanhes, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie pédiatrique - CHU Reims, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [CH Boulogne/Mer], CH Boulogne sur Mer, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de cancérologie et d'hématologie [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Service d'Hématologie [CH Annecy], CH Annecy, Service d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [ CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service d'Hématologie et thérapie cellulaire [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hématologie [CH Mulhouse], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'Hématologie [CH Perpignan], CH Perpignan, Service d'Hématologie [CH Argenteuil], CH Argenteuil, Service d'hématologie (CH de la Côte Basque), Centre Hospitalier de la Côte Basque (CHCB), Département d'Oncologie Médicale et d'Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie [CH Béziers], CH Béziers, Service d'Hématologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Service d'Hématologie Biologique [CHU Nantes], Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’hématologie Clinique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Celgene for providing azacitidine, lenalidomide and financial support for the monitoring., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [Saint-Etienne], Institut de Cancérologie de la Loire [Saint-Etienne], Le CHCB, Centre Hospitalier de la Côte Basque, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Hématologie Biologique [CHU Toulouse], CHU Toulouse [Toulouse]-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Bernardo, Elizabeth, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
Oncology, Male, medicine.medical_specialty, Azacitidine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Internal medicine, Medicine, Humans, Lenalidomide, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Hematology, business.industry, Myeloid leukemia, Middle Aged, medicine.disease, 3. Good health, Lymphoma, Thalidomide, Survival Rate, Leukemia, Haematopoiesis, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Immunology, Female, business, 030215 immunology, medicine.drug
Abstract

Maintenance therapy with alternating azacitidine and lenalidomide in elderly fit patients with poor prognosis acute myeloid leukemia: a phase II multicentre FILO trial

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results