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3. Molecular landscape of mature B‐cell lymphoproliferative disorders with BCL3‐translocation: A Groupe Francophone de Cytogénétique Hématologique (GFCH)/French Innovative Leukemia Organization (FILO) study.

Author

Véronèse, Lauren, Bensaber, Hedi, Dannus, Louis‐Thomas, Giannone, Gaetan, Choiset, Christopher, Grimpret, Corentin, Abermil, Nassera, Balducci, Estelle, Bidet, Audrey, Chapiro, Elise, Couronné, Lucile, Daudignon, Agnès, Douet‐Gilbert, Nathalie, Eclache, Virginie, Gaillard, Baptiste, Gaillard, Jean‐Baptiste, Hsoumi, Faten, Lefebvre, Christine, Nadal, Nathalie, and Mozziconacci, Marie‐Joelle

Published
2024
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4. Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial

Author

Le Gouill, Steven, Morschhauser, Franck, Chiron, David, Bouabdallah, Krimo, Cartron, Guillaume, Casasnovas, Olivier, Bodet-Milin, Caroline, Ragot, Sylviane, Bossard, Céline, Nadal, Nathalie, Herbaux, Charles, Tessoulin, Benoit, Tchernonog, Emmanuelle, Rossi, Cédric, McCulloch, Rory, Gastinne, Thomas, Callanan, Mary B., and Rule, Simon

Published
2021
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5. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11

Author

Lafage-Pochitaloff, Marina, Gerby, Bastien, Baccini, Véronique, Largeaud, Laetitia, Fregona, Vincent, Prade, Naïs, Juvin, Pierre-Yves, Jamrog, Laura, Bories, Pierre, Hébrard, Sylvie, Lagarde, Stéphanie, Mas, Véronique Mansat-De, Dovey, Oliver M, Yusa, Kosuke, Vassiliou, George S, Jansen, Joop H., Tekath, Tobias, Rombaut, David, Ameye, Geneviève, Barin, Carole, Bidet, Audrey, Boudjarane, John, Collonge-Rame, Marie-Agnès, Gervais, Carine, Ittel, Antoine, Lefebvre, Christine, Luquet, Isabelle, Michaux, Lucienne, Nadal, Nathalie, Poirel, Hélène A., Radford-Weiss, Isabelle, Ribourtout, Bénédicte, Richebourg, Steven, Struski, Stéphanie, Terré, Christine, Tigaud, Isabelle, Penther, Dominique, Eclache, Virginie, Fontenay, Michaela, Broccardo, Cyril, and Delabesse, Eric

Published
2021
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6. Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53

Author

Chapiro, Elise, Pramil, Elodie, Diop, M'boyba, Roos-Weil, Damien, Dillard, Clémentine, Gabillaud, Clémentine, Maloum, Karim, Settegrana, Catherine, Baseggio, Lucile, Lesesve, Jean-François, Yon, Mélanie, Jondreville, Ludovic, Lesty, Claude, Davi, Frédéric, Le Garff-Tavernier, Magali, Droin, Nathalie, Dessen, Philippe, Algrin, Caroline, Leblond, Véronique, Gabarre, Jean, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stéphanie, Collonge-Rame, Marie-Agnès, Quilichini, Benoit, Fert-Ferrer, Sandra, Auger, Nathalie, Radford-Weiss, Isabelle, Wagner, Lena, Scheinost, Sebastian, Zenz, Thorsten, Susin, Santos A., Bernard, Olivier A., and Nguyen-Khac, Florence

Published
2019
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7. The Broad Spectrum of TP53 Mutations in CLL : Evidence of Multiclonality and Novel Mutation Hotspots

Author

Lazarian, Gregory, Leroy, Bernard, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Tueur, Giulia, Ameur, Adam, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, Soussi, Thierry, Lazarian, Gregory, Leroy, Bernard, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Tueur, Giulia, Ameur, Adam, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, and Soussi, Thierry

Abstract

TP53 aberrations are a major predictive factor of resistance to chemoimmunotherapy in chronic lymphocytic leukemia (CLL), and an assessment of them before each line of treatment is required for theranostic stratification. Acquisition of subclonal TP53 abnormalities underlies the evolution of CLL. To better characterize the distribution, combination, and impact of TP53 variants in CLL, 1,056 TP53 variants collected from 683 patients included in a multicenter collaborative study in France were analyzed and compared to UMD_CLL, a dataset built from published articles collectively providing 5,173 TP53 variants detected in 3,808 patients. Our analysis confirmed the presence of several CLL-specific hotspot mutations, including a two-base pair deletion in codon 209 and a missense variant at codon 234, the latter being associated with alkylating treatment. Our analysis also identified a novel CLL-specific variant in the splice acceptor signal of intron 6 leading to the use of a cryptic splice site, similarly utilized by TP53 to generate p53psi, a naturally truncated p53 isoform localized in the mitochondria. Examination of both UMD_CLL and several recently released large-scale genomic analyses of CLL patients confirmed that this splice variant is highly enriched in this disease when compared to other cancer types. Using a TP53-specific single-nucleotide polymorphism, we also confirmed that copy-neutral loss of heterozygosity is frequent in CLL. This event can lead to misinterpretation of TP53 status. Unlike other cancers, CLL displayed a high proportion of patients harboring multiple TP53 variants. Using both in silico analysis and single molecule smart sequencing, we demonstrated the coexistence of distinct subclones harboring mutations on distinct alleles. In summary, our study provides a detailed TP53 mutational architecture in CLL and gives insights into how treatments may shape the genetic landscape of CLL patients.

Published
2023
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8. “Double‐hit” chronic lymphocytic leukemia: An aggressive subgroup with 17p deletion and 8q24 gain

Author

Chapiro, Elise, Lesty, Claude, Gabillaud, Clémentine, Durot, Eric, Bouzy, Simon, Armand, Marine, Le Garff‐Tavernier, Magali, Bougacha, Nadia, Struski, Stéphanie, Bidet, Audrey, Laharanne, Elodie, Barin, Carole, Veronese, Lauren, Prié, Nolwen, Eclache, Virginie, Gaillard, Baptiste, Michaux, Lucienne, Lefebvre, Christine, Gaillard, Jean‐Baptiste, Terré, Christine, Penther, Dominique, Bastard, Christian, Nadal, Nathalie, Fert‐Ferrer, Sandra, Auger, Nathalie, Godon, Catherine, Sutton, Laurent, Tournilhac, Olivier, Susin, Santos A., and Nguyen‐Khac, Florence

Published
2018
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10. Chromosomal translocations involving the IGH@ locus in B-cell precursor acute lymphoblastic leukemia: 29 new cases and a review of the literature

Author

Chapiro, Elise, Radford-Weiss, Isabelle, Cung, Hong-Anh, Dastugue, Nicole, Nadal, Nathalie, Taviaux, Sylvie, Barin, Carole, Struski, Stephanie, Talmant, Pascaline, Vandenberghe, Peter, Mozziconacci, Marie-Joelle, Tigaud, Isabelle, Lefebvre, Christine, Penther, Dominique, Bastard, Christian, Lippert, Eric, Mugneret, Francine, Romana, Serge, Bernard, Olivier A., Harrison, Christine J., Russell, Lisa J., and Nguyen-Khac, Florence

Published
2013
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11. TP53 mutations at codon 234 are associated with chlorambucil treatment in chronic lymphocytic leukemia

Author

Lazarian, Gregory, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Lode, Laurence, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, Soussi, Thierry, Lazarian, Gregory, Theves, Floriane, Hormi, Myriam, Letestu, Remi, Eclache, Virginie, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frederic, Delabesse, Eric, Estienne, Marie-Helene, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Lode, Laurence, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cedric, Poulain, Stephanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valerie, Cymbalista, Florence, Baran-Marszak, Fanny, and Soussi, Thierry

Published
2022
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12. The presence of a chromosomal abnormality in cytopenia without dysplasia identifies a category of high‐risk clonal cytopenia of unknown significance.

Author

Brett, Victor‐Emmanuel, Lechevalier, Nicolas, Trimoreau, Franck, Dussiau, Charles, Dimicoli‐Salazar, Sophie, Coster, Lucie, Luquet, Isabelle, Nadal, Nathalie, Ribourtout, Bénédicte, Chapiro, Elise, Lefebvre, Christine, Tondeur, Sylvie, Balducci, Estelle, Nguyen‐Khac, Florence, Borie, Claire, Radford‐Weiss, Isabelle, Barin, Carole, Eclache, Virginie, Mansier, Olivier, and Bidet, Audrey

Published
2023
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14. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11

Author

Lafage-Pochitaloff, Marina, primary, Gerby, Bastien, additional, Baccini, Véronique, additional, Largeaud, Laetitia, additional, Fregona, Vincent, additional, Prade, Naïs, additional, Juvin, Pierre-Yves, additional, Jamrog, Laura, additional, Bories, Pierre, additional, Hébrard, Sylvie, additional, Lagarde, Stéphanie, additional, Mansat-De Mas, Véronique, additional, Dovey, Oliver M., additional, Yusa, Kosuke, additional, Vassiliou, George S., additional, Jansen, Joop H., additional, Tekath, Tobias, additional, Rombaut, David, additional, Ameye, Geneviève, additional, Barin, Carole, additional, Bidet, Audrey, additional, Boudjarane, John, additional, Collonge-Rame, Marie-Agnès, additional, Gervais, Carine, additional, Ittel, Antoine, additional, Lefebvre, Christine, additional, Luquet, Isabelle, additional, Michaux, Lucienne, additional, Nadal, Nathalie, additional, Poirel, Hélène A., additional, Radford-Weiss, Isabelle, additional, Ribourtout, Bénédicte, additional, Richebourg, Steven, additional, Struski, Stéphanie, additional, Terré, Christine, additional, Tigaud, Isabelle, additional, Penther, Dominique, additional, Eclache, Virginie, additional, Fontenay, Michaela, additional, Broccardo, Cyril, additional, and Delabesse,, Eric, additional

Published
2022
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15. Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogénétique Hématologique study

Author

Coyaud, Etienne, Struski, Stephanie, Prade, Nais, Familiades, Julien, Eichner, Ruth, Quelen, Cathy, Bousquet, Marina, Mugneret, Francine, Talmant, Pascaline, Pages, Marie-Pierre, Lefebvre, Christine, Penther, Dominique, Lippert, Eric, Nadal, Nathalie, Taviaux, Sylvie, Poppe, Bruce, Luquet, Isabelle, Baranger, Laurence, Eclache, Virginie, Radford, Isabelle, Barin, Carole, Mozziconacci, Marie-Joëlle, Lafage-Pochitaloff, Marina, Antoine-Poirel, Hélène, Charrin, Christiane, Perot, Christine, Terre, Christine, Brousset, Pierre, Dastugue, Nicole, and Broccardo, Cyril

Published
2010
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17. Clinical and biological features of B‐cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities

Author

Gailllard, Baptiste, Cornillet‐Lefebvre, Pascale, Le, Quoc‐Hung, Maloum, Karim, Pannetier, Mélanie, Lecoq‐Lafon, Carinne, Grange, Béatrice, Jondreville, Ludovic, Michaux, Lucienne, Nadal, Nathalie, Ittel, Antoine, Luquet, Isabelle, Struski, Stéphanie, Lefebvre, Christine, Gaillard, Jean‐Baptiste, Lafage‐Pochitaloff, Marina, Balducci, Estelle, Penther, Dominique, Barin, Carole, Collonge‐Rame, Marie Agnès, Jimenez‐Poquet, Mélanie, Richebourg, Steven, Defasque, Sabine, Radford‐Weiss, Isabelle, Bidet, Audrey, Susin, Santos, Nguyen‐Khac, Florence, Chapiro, Elise, Lemaire, Pierre, Hôpital universitaire Robert Debré [Reims], Service d'Hématologie Biologique [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), CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), University Hospitals Leuven [Leuven], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Strasbourg, 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-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Unité de Génétique Chromosomique [Montpellier], Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée [Montpellier], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Paul Brousse, Département de génétique [CHU Rouen] (Centre Normandie de Génomique et de Médecine Personnalisée), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laborizon Abo+, Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval), Laboratoire CERBA [Saint Ouen l'Aumône], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Gestionnaire, HAL Sorbonne Université 5, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Paris (UP)

Subjects
Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, CDK6, Trisomy, CD5 Antigens, Translocation, Genetic, prolymphocytic cell, Humans, TP53, In Situ Hybridization, Fluorescence, Aged, Aged, 80 and over, Chromosome Aberrations, Splenic Neoplasms, Bronchial Neoplasms, Cell Differentiation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cyclin-Dependent Kinase 6, Lymphoma, B-Cell, Marginal Zone, Middle Aged, Genes, p53, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, marginal zone lymphoma, CD5, Phenotype, Tertiary Lymphoid Structures, Mutation, Female, Tumor Suppressor Protein p53, Immunoglobulin Heavy Chains
Abstract

International audience; A translocation involving the cyclin‐dependent kinase 6 (CDK6) gene [t(CDK6)] is a rare but recurrent abnormality in B‐cell neoplasms. To further characterise this aberration, we studied 57 cases; the largest series reported to date. Fluorescence in situ hybridisation analysis confirmed the involvement of CDK6 in all cases, including t(2;7)(p11;q21) immunoglobulin kappa locus (IGK)/CDK6 (n = 51), t(7;14)(q21;q32) CDK6/immunoglobulin heavy locus (IGH) (n = 2) and the previously undescribed t(7;14)(q21;q11) CDK6/T‐cell receptor alpha locus (TRA)/T‐cell receptor delta locus (TRD) (n = 4). In total, 10 patients were diagnosed with chronic lymphocytic leukaemia, monoclonal B‐cell lymphocytosis or small lymphocytic lymphoma, and 47 had small B‐cell lymphoma (SmBL) including 36 cases of marginal zone lymphoma (MZL; 34 splenic MZLs, one nodal MZL and one bronchus‐associated lymphoid tissue lymphoma). In all, 18 of the 26 cytologically reviewed cases of MZL (69%) had an atypical aspect with prolymphocytic cells. Among the 47 patients with MZL/SmBL, CD5 expression was found in 26 (55%) and the tumour protein p53 (TP53) deletion in 22 (47%). The TP53 gene was mutated in 10/30 (33%); the 7q deletion was detected in only one case, and no Notch receptor 2 (NOTCH2) mutations were found. Immunoglobulin heavy‐chain variable‐region (IGHV) locus sequencing revealed that none harboured an IGHV1‐02*04 gene. Overall survival was 82% at 10 years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B‐cell lymphomas with distinctive features.

Published
2020

18. Ibrutinib, Obinutuzumab And Venetoclax In Relapsed and Untreated Patients with Mantle-Cell Lymphoma, a phase I/II trial

Author

Le Gouill, Steven, Morschhauser, Franck, Chiron, David, Bouabdallah, Krimo, Cartron, Guillaume, Casasnovas, Olivier, Bodet-Milin, Caroline, Ragot, Sylviane, Bossard, Céline, Nadal, Nathalie, Herbaux, Charles, Tessoulin, Benoit, Tchernonog, Emmanuelle, Rossi, Cédric, Mc Culloch, Rory, Gastinne, Thomas, Callanan, Mary, Rule, Simon, 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), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pessac, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Saint Eloi (CHRU Montpellier), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Plymouth University, 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), 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 [Lille] (CHRU Lille)-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and CHU Saint-Eloi

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract

International audience; Ibrutinib, obinutuzumab plus venetoclax demonstrate synergy in pre-clinical models of mantle-cell lymphoma (MCL). OAsIs (NCT02558816), a single-arm multi-center prospective phase I/II trial, aimed to determine the maximum tolerated dose (MTD) of venetoclax in combination with fixed doses of ibrutinib and obinutuzumab, in relapsed MCL patients. At the venetoclax MTD, extension cohorts were opened for relapsed and untreated patients. Safety and efficacy were secondary objectives. Minimal residual disease (MRD) was assessed by allele-specific oligonucleotide-quantitative polymerase chain reaction (ASO-qPCR). Between Oct 14, 2015 to May 29, 2018, forty-eight patients were enrolled. No dose limiting toxicity (DLT) was reported, and venetoclax at 400mg per day was chosen for extension. Eighteen (75%) relapsed and 8 (53%) untreated patients experienced grade 3/4 adverse events (AEs). The complete response rate assessed by positron-emission tomography at the end of cycle 6 was 67% in relapsed and 86.6% in untreated patients. MRD clearance for evaluable patients was seen in 71.5% of relapsed (10 out of 14) and 100% of untreated MRD-evaluable patients (n=12), at the end of three cycles. The median follow-up (mFU) for relapsed patients was 17 months (range, 10 to 35). The 2-years PFS was 69.5% (95% CI, 52.9-91.4%) and 68.6% (95% CI, 49.5-95.1%) for OS. The mFU was 14 months (range, 5 to 19) for untreated patients, the 1-year PFS was 93.3% (95% CI, 81.5-100%). Obinutuzimab, ibrutinib and venetoclax combination is well tolerated and provides high response rates including at the molecular level in relapsed and untreated MCL patients.

Published
2020

19. Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21)

Author

Burlet, Bénédicte, primary, Ramla, Selim, additional, Fournier, Cyril, additional, Abrey-Recalde, Maria Jimena, additional, Sauter, Camille, additional, Chrétien, Marie-Lorraine, additional, Rossi, Cédric, additional, Duffourd, Yannis, additional, Ragot, Sylviane, additional, Buriller, Céline, additional, Tournier, Benjamin, additional, Chapusot, Caroline, additional, Nadal, Nathalie, additional, Racine, Jessica, additional, Guy, Julien, additional, Bailly, François, additional, Martin, Laurent, additional, Casasnovas, Olivier, additional, Bastie, Jean-Noël, additional, Caillot, Denis, additional, Albuisson, Juliette, additional, Broccardo, Cyril, additional, Thieblemont, Catherine, additional, Delva, Laurent, additional, Maynadié, Marc, additional, Aucagne, Romain, additional, and Callanan, Mary B., additional

Published
2021
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20. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Author

Duhoux, Francois P., Ameye, Geneviève, Montano-Almendras, Carmen P., Bahloula, Khadija, Mozziconacci, Marie J., Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Auger, Nathalie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Roche-Lestienne, Catherine, Latinne, Dominique, Libouton, Jeanne M., Demoulin, Jean-Baptiste, and Poirel, Hélène A.

Published
2012
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21. B-ALL With t(5;14)(q31;q32); IGH-IL3 Rearrangement and Eosinophilia: A Comprehensive Analysis of a Peculiar IGH-Rearranged B-ALL

Author

Fournier, Benjamin, primary, Balducci, Estelle, additional, Duployez, Nicolas, additional, Clappier, Emmanuelle, additional, Cuccuini, Wendy, additional, Arfeuille, Chloé, additional, Caye-Eude, Aurélie, additional, Delabesse, Eric, additional, Bottollier-Lemallaz Colomb, Elodie, additional, Nebral, Karin, additional, Chrétien, Marie-Lorraine, additional, Derrieux, Coralie, additional, Cabannes-Hamy, Aurélie, additional, Dumezy, Florent, additional, Etancelin, Pascaline, additional, Fenneteau, Odile, additional, Frayfer, Jamile, additional, Gourmel, Antoine, additional, Loosveld, Marie, additional, Michel, Gérard, additional, Nadal, Nathalie, additional, Penther, Dominique, additional, Tigaud, Isabelle, additional, Fournier, Elise, additional, Reismüller, Bettina, additional, Attarbaschi, Andishe, additional, Lafage-Pochitaloff, Marina, additional, and Baruchel, André, additional

Published
2019
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22. Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving and MYC and TP53

Author

Chapiro, Elise, Pramil, Elodie, Diop, M'boyba, Roos-Weil, Damien, Dillard, Clémentine, Gabillaud, Clémentine, Maloum, Karim, Settegrana, Catherine, Baseggio, Lucile, Lesesve, Jean-François, Yon, Mélanie, Jondreville, Ludovic, Lesty, Claude, Davi, Frederic, Le Garff-Tavernier, Magali, Droin, Nathalie, Dessen, Philippe, Algrin, Caroline, Leblond, Veronique, Gabarre, Jean, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stephanie, Collonge-Rame, Marie-Agnès, et al, and University of Zurich

Subjects
1307 Cell Biology, 2403 Immunology, 1303 Biochemistry, 10032 Clinic for Oncology and Hematology, 2720 Hematology, 610 Medicine & health
Published
2019

23. Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving and MYC and TP53

Author

Chapiro, Elise; https://orcid.org/0000-0003-3427-7596, Pramil, Elodie, Diop, M'boyba, Roos-Weil, Damien; https://orcid.org/0000-0002-7767-755X, Dillard, Clémentine, Gabillaud, Clémentine, Maloum, Karim; https://orcid.org/0000-0001-8864-4801, Settegrana, Catherine, Baseggio, Lucile; https://orcid.org/0000-0001-7543-6480, Lesesve, Jean-François, Yon, Mélanie, Jondreville, Ludovic, Lesty, Claude, Davi, Frederic; https://orcid.org/0000-0002-3764-063X, Le Garff-Tavernier, Magali; https://orcid.org/0000-0002-3131-3240, Droin, Nathalie, Dessen, Philippe, Algrin, Caroline, Leblond, Veronique, Gabarre, Jean, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stephanie, Collonge-Rame, Marie-Agnès, et al, Chapiro, Elise; https://orcid.org/0000-0003-3427-7596, Pramil, Elodie, Diop, M'boyba, Roos-Weil, Damien; https://orcid.org/0000-0002-7767-755X, Dillard, Clémentine, Gabillaud, Clémentine, Maloum, Karim; https://orcid.org/0000-0001-8864-4801, Settegrana, Catherine, Baseggio, Lucile; https://orcid.org/0000-0001-7543-6480, Lesesve, Jean-François, Yon, Mélanie, Jondreville, Ludovic, Lesty, Claude, Davi, Frederic; https://orcid.org/0000-0002-3764-063X, Le Garff-Tavernier, Magali; https://orcid.org/0000-0002-3131-3240, Droin, Nathalie, Dessen, Philippe, Algrin, Caroline, Leblond, Veronique, Gabarre, Jean, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stephanie, Collonge-Rame, Marie-Agnès, and et al

Abstract

B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessment of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex ({greater than or equal to}3 abnormalities) in 73% of the patients and highly complex (5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving [t()] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six of the 34 patients (76%) exhibit aberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in , , , , , , , , and The majority of B-PLL used the or subgroups (89%), and displayed significantly mutated genes (79%). We identified three distinct cytogenetic risk groups: low-risk (no aberration), intermediate-risk ( aberration but no del17p), and high-risk ( aberration and del17p) (p=.0006). drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif (BET) inhibitor targeting ) was associated with significantly lower viability of B-PLL cells harboring a t(). We conclude that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting may be a useful treatment option in this disease.

Published
2019

24. MOESM1 of Potential added value of a RT-qPCR method of SOX 11 expression, in the context of a multidisciplinary diagnostic assessment of B cell malignancies

Author

Magne, Julien, AlizĂŠe Jenvrin, Chauchet, Adrien, Casasnovas, Olivier, Donzel, Anne, Jego, Laurence, Aral, Bernard, Guy, Julien, Nadal, Nathalie, Vernerey, Dewi, Callier, Patrick, Garnache-Ottou, Francine, and Ferrand, Christophe

Subjects
Data_FILES
Abstract

Additional file 1. Figures.

Published
2018
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25. The Broad Spectrum of TP53 Variants in CLL: NGS Analysis of 573 Pathogenic TP53 Variants

Author

Lazarian, Gregory, primary, Theves, Floriane, additional, Hormi, Myriam, additional, Eclache, Virginie, additional, Poulain, Stéphanie, additional, Bidet, Audrey, additional, Pastoret, Cedric, additional, Veronese, Lauren, additional, Delabesse, Eric, additional, Estienne, Marie-Hélène, additional, Nadal, Nathalie, additional, Davi, Frederic, additional, Nguyen-Khac, Florence, additional, Lode, Laurence, additional, Sujobert, Pierre, additional, Naguib, Dina, additional, Raynaud, Sophie, additional, Giraudier, Stephane, additional, Kosmider, Olivier, additional, Etancelin, Pascaline, additional, Cornillet-Lefebvre, Pascale, additional, Miguet, Laurent, additional, Leblond, Veronique, additional, Letestu, Remi, additional, Soussi, Thierry, additional, Cymbalista, Florence, additional, and Baran-Marszak, Fanny, additional

Published
2019
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26. The CADM1tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11

Author

Lafage-Pochitaloff, Marina, Gerby, Bastien, Baccini, Véronique, Largeaud, Laetitia, Fregona, Vincent, Prade, Naïs, Juvin, Pierre-Yves, Jamrog, Laura, Bories, Pierre, Hébrard, Sylvie, Lagarde, Stéphanie, Mansat-De Mas, Véronique, Dovey, Oliver M., Yusa, Kosuke, Vassiliou, George S., Jansen, Joop H., Tekath, Tobias, Rombaut, David, Ameye, Geneviève, Barin, Carole, Bidet, Audrey, Boudjarane, John, Collonge-Rame, Marie-Agnès, Gervais, Carine, Ittel, Antoine, Lefebvre, Christine, Luquet, Isabelle, Michaux, Lucienne, Nadal, Nathalie, Poirel, Hélène A., Radford-Weiss, Isabelle, Ribourtout, Bénédicte, Richebourg, Steven, Struski, Stéphanie, Terré, Christine, Tigaud, Isabelle, Penther, Dominique, Eclache, Virginie, Fontenay, Michaela, Broccardo, Cyril, and Delabesse, Eric

Abstract

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBLgenes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1(also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBLand mutations of ASXL1, SF3B1, and CBL, we show that CADM1may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.

Published
2022
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27. Poor prognosis of chromosome 7 clonal aberrations in Philadelphia-negative metaphases and relevance of potential underlying myelodysplastic features in chronic myeloid leukemia

Author

Bidet, Audrey, primary, Dulucq, Stéphanie, additional, Smol, Thomas, additional, Marceau-Renaut, Alice, additional, Morisset, Stéphane, additional, Coiteux, Valérie, additional, Noël-Walter, Marie-Pierre, additional, Nicolini, Franck-Emmanuel, additional, Tigaud, Isabelle, additional, Luquet, Isabelle, additional, Struski, Stéphanie, additional, Gaillard, Baptiste, additional, Penther, Dominique, additional, Tondeur, Sylvie, additional, Nadal, Nathalie, additional, Hermet, Eric, additional, Véronèse, Lauren, additional, Réa, Delphine, additional, Gervais, Carine, additional, Theisen, Olivier, additional, Terré, Christine, additional, Cony-Makhoul, Pascale, additional, Lefebvre, Christine, additional, Gaillard, Jean-Baptiste, additional, Radford, Isabelle, additional, Vervaeke, Anne-Laure, additional, Barin, Carole, additional, Chapiro, Elise, additional, Nguyen-Khac, Florence, additional, Etienne, Gabriel, additional, Preudhomme, Claude, additional, Mahon, François Xavier, additional, and Roche-Lestienne, Catherine, additional

Published
2018
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28. Clinical and biological features of B‐cell neoplasms with CDK6 translocations: an association with a subgroup of splenic marginal zone lymphomas displaying frequent CD5 expression, prolymphocytic cells, and TP53 abnormalities.

Author

Gailllard, Baptiste, Cornillet‐Lefebvre, Pascale, Le, Quoc‐Hung, Maloum, Karim, Pannetier, Mélanie, Lecoq‐Lafon, Carinne, Grange, Béatrice, Jondreville, Ludovic, Michaux, Lucienne, Nadal, Nathalie, Ittel, Antoine, Luquet, Isabelle, Struski, Stéphanie, Lefebvre, Christine, Gaillard, Jean‐Baptiste, Lafage‐Pochitaloff, Marina, Balducci, Estelle, Penther, Dominique, Barin, Carole, and Collonge‐Rame, Marie Agnès

Subjects
MUCOSA-associated lymphoid tissue lymphoma, TUMORS, P53 protein, LYMPHOMAS, LYMPHOCYTIC leukemia, CHRONIC leukemia
Abstract

Summary: A translocation involving the cyclin‐dependent kinase 6 (CDK6) gene [t(CDK6)] is a rare but recurrent abnormality in B‐cell neoplasms. To further characterise this aberration, we studied 57 cases; the largest series reported to date. Fluorescence in situ hybridisation analysis confirmed the involvement of CDK6 in all cases, including t(2;7)(p11;q21) immunoglobulin kappa locus (IGK)/CDK6 (n = 51), t(7;14)(q21;q32) CDK6/immunoglobulin heavy locus (IGH) (n = 2) and the previously undescribed t(7;14)(q21;q11) CDK6/T‐cell receptor alpha locus (TRA)/T‐cell receptor delta locus (TRD) (n = 4). In total, 10 patients were diagnosed with chronic lymphocytic leukaemia, monoclonal B‐cell lymphocytosis or small lymphocytic lymphoma, and 47 had small B‐cell lymphoma (SmBL) including 36 cases of marginal zone lymphoma (MZL; 34 splenic MZLs, one nodal MZL and one bronchus‐associated lymphoid tissue lymphoma). In all, 18 of the 26 cytologically reviewed cases of MZL (69%) had an atypical aspect with prolymphocytic cells. Among the 47 patients with MZL/SmBL, CD5 expression was found in 26 (55%) and the tumour protein p53 (TP53) deletion in 22 (47%). The TP53 gene was mutated in 10/30 (33%); the 7q deletion was detected in only one case, and no Notch receptor 2 (NOTCH2) mutations were found. Immunoglobulin heavy‐chain variable‐region (IGHV) locus sequencing revealed that none harboured an IGHV1‐02*04 gene. Overall survival was 82% at 10 years and not influenced by TP53 aberration. Our present findings suggest that most t(CDK6)+ neoplasms correspond to a particular subgroup of indolent marginal zone B‐cell lymphomas with distinctive features. [ABSTRACT FROM AUTHOR]

Published
2021
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29. Genetic Characterization of B-Cell Prolymphocytic Leukemia (B-PLL): A Hierarchical Prognostic Model Involving MYC and TP53 Abnormalities. on Behalf of the Groupe Francophone De Cytogenetique Hematologique (GFCH) and the French Innovative Leukemia Organization (FILO) Group

Author

Chapiro, Elise, primary, Roos-Weil, Damien, additional, Bougacha, Nadia, additional, Gabillaud, Clementine, additional, Dillard, Clémentine, additional, Pramil, Elodie, additional, Yon, Melanie, additional, Maloum, Karim, additional, Settegrana, Catherine, additional, Baseggio, Lucile, additional, Lesty, Claude, additional, Davi, Frederic, additional, Le Garff-Tavernier, Magali, additional, Diop, M'boyba Khadija, additional, Droin, Nathalie M, additional, Dessen, Philippe, additional, Leblond, Veronique, additional, Algrin, Caroline, additional, Bouzy, Simon, additional, Eclache, Virginie, additional, Gaillard, Baptiste, additional, Callet-Bauchu, Evelyne, additional, Muller, Marc, additional, Lefebvre, Christine, additional, Nadal, Nathalie, additional, Ittel, Antoine, additional, Struski, Stéphanie, additional, Collonge-Rame, Marie-Agnes, additional, Quilichini, Benoit, additional, Fert-Ferrer, Sandra, additional, Auger, Nathalie, additional, Radford-Weiss, Isabelle, additional, Wagner, Lena, additional, Scheinost, Sebastian, additional, Zenz, Thorsten, additional, Susin, Santos, additional, Bernard, Olivier, additional, and Nguyen-Khac, Florence, additional

Published
2018
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32. Isolated isochromosomes i(X)(p10) and idic(X)(q13) are associated with myeloid malignancies and dysplastic features.

Author

Penther, Dominique, Etancelin, Pascaline, Lusina, Daniel, Bidet, Audrey, Quilichini, Benoit, Gaillard, Baptiste, Rafdord‐Weiss, Isabelle, Mozziconacci, Marie Joelle, Ittel, Antoine, Roche‐Lestienne, Catherine, Barin, Carole, Soler, Gwendoline, Daudignon, Agnes, Nadal, Nathalie, Chapiro, Elise, Lefebvre, Christine, Godon, Catherine, Nadeau, Gwenael, Mugneret, Francine, and Richebourg, Steven

Published
2019
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33. Cytogenetics in the management of lymphomas and lymphoproliferative disorders in adults and children: an update by the Groupe francophone de cytogénétique hématologique (GFCH).

Author

UCL - (SLuc) Centre de génétique médicale UCL, Lefebvre, Christine, Callet-Bauchu, Evelyne, Chapiro, Elise, Nadal, Nathalie, Penther, Dominique, Poirel, Hélène-Antoine, UCL - (SLuc) Centre de génétique médicale UCL, Lefebvre, Christine, Callet-Bauchu, Evelyne, Chapiro, Elise, Nadal, Nathalie, Penther, Dominique, and Poirel, Hélène-Antoine

Abstract

Non-Hodgkin's lymphomas and lymphoproliferative disorders include a high number of heterogeneous entities, described in the 2008 WHO classification. This classification reflects the crucial role of a multidisciplinary approach which integrates cytogenetic results both for the notion of clonality and for differential diagnosis between these entities. The prognostic impact of some cytogenetic abnormalities or genome complexity is also confirmed for many of these entities. Novel provisional entities have been described, such as BCLU (B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) for which karyotype is critical to distinguish BCLU from Burkitt's lymphoma. The karyotype can be established from any tumour or liquid infiltrated by lymphoma cells. Recent adaptations of technics for cellular cultures according to the subtype of known (or suspected) lymphoma have significantly improved the percentage of informative karyotypes. Conventional karyotypes remain the best technical approach recommended for most of these subtypes. Interphase and/or metaphase FISH also represents a solid and rapid approach, because of the significant number of recurrent (sometimes specific) rearrangements of these entities. Next generation sequencing technologies contribute to enrich genomic data and substantially improve the understanding of oncogenic mechanisms underlying these lymphoid malignancies. Some molecular biomarkers are already part of the diagnostic process (for example, somatic mutation of MYD88 in Waldenström disease) thus reinforcing the essential principle of a multidisciplinary approach for the diagnosis of all the mature lymphoid malignancies.

Published
2016

35. Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYCand TP53

Author

Chapiro, Elise, Pramil, Elodie, Diop, M'boyba, Roos-Weil, Damien, Dillard, Clémentine, Gabillaud, Clémentine, Maloum, Karim, Settegrana, Catherine, Baseggio, Lucile, Lesesve, Jean-François, Yon, Mélanie, Jondreville, Ludovic, Lesty, Claude, Davi, Frédéric, Le Garff-Tavernier, Magali, Droin, Nathalie, Dessen, Philippe, Algrin, Caroline, Leblond, Véronique, Gabarre, Jean, Bouzy, Simon, Eclache, Virginie, Gaillard, Baptiste, Callet-Bauchu, Evelyne, Muller, Marc, Lefebvre, Christine, Nadal, Nathalie, Ittel, Antoine, Struski, Stéphanie, Collonge-Rame, Marie-Agnès, Quilichini, Benoit, Fert-Ferrer, Sandra, Auger, Nathalie, Radford-Weiss, Isabelle, Wagner, Lena, Scheinost, Sebastian, Zenz, Thorsten, Susin, Santos A., Bernard, Olivier A., and Nguyen-Khac, Florence

Abstract

B-cell prolymphocytic leukemia (B-PLL) is a rare hematological disorder whose underlying oncogenic mechanisms are poorly understood. Our cytogenetic and molecular assessments of 34 patients with B-PLL revealed several disease-specific features and potential therapeutic targets. The karyotype was complex (≥3 abnormalities) in 73% of the patients and highly complex (≥5 abnormalities) in 45%. The most frequent chromosomal aberrations were translocations involving MYC[t(MYC)] (62%), deletion (del)17p (38%), trisomy (tri)18 (30%), del13q (29%), tri3 (24%), tri12 (24%), and del8p (23%). Twenty-six (76%) of the 34 patients exhibited an MYCaberration, resulting from mutually exclusive translocations or gains. Whole-exome sequencing revealed frequent mutations in TP53, MYD88, BCOR, MYC, SF3B1, SETD2, CHD2, CXCR4, and BCLAF1. The majority of B-PLL used the IGHV3or IGHV4subgroups (89%) and displayed significantly mutated IGHVgenes (79%). We identified 3 distinct cytogenetic risk groups: low risk (no MYCaberration), intermediate risk (MYCaberration but no del17p), and high risk (MYCaberration and del17p) (P= .0006). In vitro drug response profiling revealed that the combination of a B-cell receptor or BCL2 inhibitor with OTX015 (a bromodomain and extra-terminal motif inhibitor targeting MYC) was associated with significantly lower viability of B-PLL cells harboring a t(MYC). We concluded that cytogenetic analysis is a useful diagnostic and prognostic tool in B-PLL. Targeting MYCmay be a useful treatment option in this disease.

Published
2019
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37. Refinement of 1p36 Alterations Not Involving PRDM16 in Myeloid and Lymphoid Malignancies

Author

Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Labis, Elise, Terré, Christine, Nadal, Nathalie, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Taviaux, Sylvie, Chapiro, Elise, Nguyen Khac, Florence, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Hematology and Oncology (BCG-HO), Lambert, Frédéric, Vikkula, Miikka, Poirel, Hélène, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, CHU de Liège - Center for Human Genetics, CHU de Nice - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Lille - Center for Human Genetics, CHU de Montpellier - Center for Human Genetics, Groupe Hospitalier Pitié-Salpétrière - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, IPG - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, Institut Paoli-Calmettes - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, Centre Hospitalier de Versailles - Center for Human Genetics, and UCL - SSS/DDUV - Institut de Duve

Subjects
Myeloid, Follicular lymphoma, lcsh:Medicine, Chromosomal translocation, CYTOGENETIC ANALYSIS, TUMOR-SUPPRESSOR GENE, Hematologic Cancers and Related Disorders, Chromosomal Disorders, Chromosome instability, hemic and lymphatic diseases, Molecular Cell Biology, lcsh:Science, In Situ Hybridization, Fluorescence, MYELODYSPLASTIC SYNDROME, Multidisciplinary, medicine.diagnostic_test, Chromosome Biology, NON-HODGKINS-LYMPHOMAS, Chromosomal Deletions and Duplications, Genomics, Hematology, Telomere, DNA-Binding Proteins, medicine.anatomical_structure, Oncology, Chromosomes, Human, Pair 1, Hematologic Neoplasms, Cytogenetic Analysis, Medicine, Research Article, medicine.medical_specialty, Chromosome Structure and Function, Biology, Polymorphism, Single Nucleotide, Cell Line, Cytogenetics, CHROMOSOMAL TRANSLOCATIONS, Complex Karyotype, medicine, Genetics, Cancer Genetics, Humans, Clinical Genetics, Chromosome Aberrations, CHRONIC LYMPHOCYTIC-LEUKEMIA, Breakpoint, lcsh:R, Biology and Life Sciences, Cancers and Neoplasms, Human Genetics, IN-SITU HYBRIDIZATION, medicine.disease, Molecular biology, COPY NUMBER, NEUROBLASTOMA, lcsh:Q, FOLLICULAR LYMPHOMA, Fluorescence in situ hybridization, Transcription Factors
Abstract

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

Published
2011

38. B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) with t(5;14)(q31;q32)/ IL3-IGH Rearrangement and Eosinophilia: A Peculiar IGH BCP-ALL

Author

Fournier, Benjamin, Balducci, Estelle, Duployez, Nicolas, Clappier, Emmanuelle, Cuccuini, Wendy, Bottolier-Colomb, Elodie, Caillot, Denis, Cave, Helene, Caye-Eude, Aurélie, Delabesse, Eric, Derrieux, Coralie, Dhedin, Nathalie, Dumezy, Florent, Etancelin, Pascaline, Fenneteau, Odile, Frayfer, Jamilé, Gourmel, Antoine, Loosveld, Marie, Michel, Gerard, Nadal, Nathalie, Oudin, Claire-Helene, Penther, Dominique, Tigaud, Isabelle, Grardel, Nathalie, Lafage, Marine, and Baruchel, Andre

Published
2017
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39. 14q deletions are associated with trisomy 12, NOTCH1 mutations and unmutated IGHV genes in chronic lymphocytic leukemia and small lymphocytic lymphoma

Author

UCL - (SLuc) Service d'hématologie, Cosson, Adrien, Chapiro, Elise, Belhouachi, Nabila, Cung, Hong-Anh, Keren, Boris, Damm, Frederik, Algrin, Caroline, Lefebvre, Christine, Fert-Ferrer, Sandra, Luquet, Isabelle, Gachard, Nathalie, Mugneret, Francine, Terre, Christine, Collonge-Rame, Marie-Agnes, Michaux, Lucienne, Rafdord-Weiss, Isabelle, Talmant, Pascaline, Veronese, Lauren, Nadal, Nathalie, Struski, Stephanie, Barin, Carole, Helias, Catherine, Lafage, Marina, Lippert, Eric, Auger, Nathalie, Eclache, Virginie, Roos-Weil, Damien, Leblond, Veronique, Settegrana, Catherine, Maloum, Karim, Davi, Frederic, Merle-Beral, Helene, Lesty, Claude, Nguyen-Khac, Florence, Groupe Francophone de Cytogénétique Hématologique, UCL - (SLuc) Service d'hématologie, Cosson, Adrien, Chapiro, Elise, Belhouachi, Nabila, Cung, Hong-Anh, Keren, Boris, Damm, Frederik, Algrin, Caroline, Lefebvre, Christine, Fert-Ferrer, Sandra, Luquet, Isabelle, Gachard, Nathalie, Mugneret, Francine, Terre, Christine, Collonge-Rame, Marie-Agnes, Michaux, Lucienne, Rafdord-Weiss, Isabelle, Talmant, Pascaline, Veronese, Lauren, Nadal, Nathalie, Struski, Stephanie, Barin, Carole, Helias, Catherine, Lafage, Marina, Lippert, Eric, Auger, Nathalie, Eclache, Virginie, Roos-Weil, Damien, Leblond, Veronique, Settegrana, Catherine, Maloum, Karim, Davi, Frederic, Merle-Beral, Helene, Lesty, Claude, Nguyen-Khac, Florence, and Groupe Francophone de Cytogénétique Hématologique

Abstract

Deletions of the long arm of chromosome 14 [del(14q)] are rare but recurrently observed in mature B-cell neoplasms, particularly in chronic lymphocytic leukemia (CLL). To further characterize this aberration, we studied 81 cases with del(14q): 54 of CLL and 27 of small lymphocytic lymphoma (SLL), the largest reported series to date. Using karyotype and fluorescence in situ hybridization (FISH), the most frequent additional abnormality was trisomy 12 (tri12), observed in 28/79 (35%) cases, followed by del13q14 (12/79, 15%), delTP53 (11/80, 14%) delATM (5/79, 6%), and del6q21 (3/76, 4%). IGHV genes were unmutated in 41/53 (77%) patients, with a high frequency of IGHV1-69 (21/52, 40%). NOTCH1 gene was mutated in 14/45 (31%) patients. There was no significant difference in cytogenetic and molecular abnormalities between CLL and SLL. Investigations using FISH and SNP-array demonstrated the heterogeneous size of the 14q deletions. However, a group with the same del(14)(q24.1q32.33) was identified in 48% of cases. In this group, tri12 (P = 0.004) and NOTCH1 mutations (P = 0.02) were significantly more frequent than in the other patients. In CLL patients with del(14q), median treatment-free survival (TFS) was 27 months. In conclusion, del(14q) is associated with tri12 and with pejorative prognostic factors: unmutated IGHV genes (with over-representation of the IGHV1-69 repertoire), NOTCH1 mutations, and a short TFS.

Published
2014

40. Value of Cytogenetic Abnormalities in Adult Patients with Philadelphia Chromosome (Ph)-Negative Acute Lymphoblastic Leukemia (ALL) Treated in the Pediatric-Inspired Trials from the Group for Research on Adult ALL (GRAALL)

Author

Lafage-Pochitaloff, Marina, primary, Baranger, Laurence, additional, Hunault, Mathilde, additional, Cuccuini, Wendy, additional, Bidet, Audrey, additional, Dastugue, Nicole, additional, Tigaud, Isabelle, additional, Henry, Catherine, additional, Gervais, Carine, additional, Penther, Dominique, additional, Lefebvre, Christine, additional, Nadal, Nathalie, additional, Mugneret, Francine, additional, Eclache, Virginie, additional, Radford, Isabelle, additional, Gachard, Nathalie, additional, Mozziconacci, Marie-Joelle, additional, Delabesse, Eric, additional, Bene, Marie C, additional, Chassevent, Agnès, additional, Beldjord, Kheira, additional, Asnafi, Vahid, additional, Huguet, Françoise, additional, Lhéritier, Véronique, additional, Ifrah, Norbert, additional, and Dombret, Hervé, additional

Published
2014
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41. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Author

UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Montano Almendras, Carmen Patricia, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO), Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Auger, Nathalie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Roche-Lestienne, Catherine, Latinne, Dominique, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Montano Almendras, Carmen Patricia, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO), Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Auger, Nathalie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Roche-Lestienne, Catherine, Latinne, Dominique, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, and Poirel, Hélène

Abstract

The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies.

Published
2012

42. PRDM16 alterations are frequently encountered in secondary acute myeloid leukemias after chemotherapy and/or radiation therapy

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, IPG, Gosselies - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Hôpital Arnaud de Villeneuve, Montpellier - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, CHU de Lille - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Auger, Nathalie, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, 13th Annual Meeting of the Belgian Society of Medical Oncology, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, IPG, Gosselies - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Hôpital Arnaud de Villeneuve, Montpellier - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, CHU de Lille - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Rack, Katrina, Mugneret, Francine, Tigaud, Isabelle, Lafage, Marina, Taviaux, Sylvie, Auger, Nathalie, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, and 13th Annual Meeting of the Belgian Society of Medical Oncology

Published
2011

43. PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Lafage, Marina, Auger, Nathalie, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, Annual Meeting of the American Society of Clinical Oncology (ASCO), UCL - SSS/IREC - Institut de recherche expérimentale et clinique, Institut Paoli-Calmettes, Marseille - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, CHU de Liège - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Nice - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, CHU Timone, Marseille - Center for Human Genetics, Institut Gustave Roussy, Villejuif - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Wlodarska, Iwona, Michaux, Lucienne, Talmant, Pascaline, Richebourg, Steven, Lippert, Eric, Speleman, Frank, Herens, Christian, Struski, Stéphanie, Raynaud, Sophie, Nadal, Nathalie, Lafage, Marina, Auger, Nathalie, Libouton, Jeanne-Marie, Demoulin, Jean-Baptiste, Poirel, Hélène, and Annual Meeting of the American Society of Clinical Oncology (ASCO)

Published
2011

44. Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, CHU de Liège - Center for Human Genetics, CHU de Nice - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Lille - Center for Human Genetics, CHU de Montpellier - Center for Human Genetics, Groupe Hospitalier Pitié-Salpétrière - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, IPG - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, Institut Paoli-Calmettes - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, Centre Hospitalier de Versailles - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Labis, Elise, Terré, Christine, Nadal, Nathalie, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Taviaux, Sylvie, Chapiro, Elise, Nguyen Khac, Florence, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Hematology and Oncology (BCG-HO), Lambert, Frédéric, Vikkula, Miikka, Poirel, Hélène, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, CHU de Liège - Center for Human Genetics, CHU de Nice - Center for Human Genetics, KULeuven - Center for Human Genetics, CHU de Lille - Center for Human Genetics, CHU de Montpellier - Center for Human Genetics, Groupe Hospitalier Pitié-Salpétrière - Center for Human Genetics, Hôpital Purpan, Toulouse - Center for Human Genetics, CHU de Bordeaux - Center for Human Genetics, UZ Ghent - Center for Human Genetics, IPG - Center for Human Genetics, CHU de Nantes - Center for Human Genetics, CHU de Dijon - Center for Human Genetics, Centre Hospitalier Lyon Sud - Center for Human Genetics, Institut Paoli-Calmettes - Center for Human Genetics, CHU Hôpital Nord, Saint-Etienne - Center for Human Genetics, Centre Hospitalier de Versailles - Center for Human Genetics, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Labis, Elise, Terré, Christine, Nadal, Nathalie, Laibe, Sophy, Mozziconacci, Marie-Joëlle, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Taviaux, Sylvie, Chapiro, Elise, Nguyen Khac, Florence, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Groupe Francophone de Cytogénétique Hématologique (GFCH), Belgian Cytogenetic Group for Hematology and Oncology (BCG-HO), Lambert, Frédéric, Vikkula, Miikka, and Poirel, Hélène

Abstract

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

Published
2011

45. Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.

Author

UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Lambert, Frédéric, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Labis, Elise, Taviaux, Sylvie, Chapiro, Elise, Nguyen-Khac, Florence, Khac, Florence Nguyen, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Nadal, Nathalie, Terré, Christine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Vikkula, Miikka, Poirel, Hélène, UCL - SSS/DDUV - Institut de Duve, Duhoux, François, Ameye, Geneviève, Lambot, Virginie, Herens, Christian, Lambert, Frédéric, Raynaud, Sophie, Wlodarska, Iwona, Michaux, Lucienne, Roche-Lestienne, Catherine, Labis, Elise, Taviaux, Sylvie, Chapiro, Elise, Nguyen-Khac, Florence, Khac, Florence Nguyen, Struski, Stéphanie, Dobbelstein, Sophie, Dastugue, Nicole, Lippert, Eric, Speleman, Frank, Van Roy, Nadine, De Weer, An, Rack, Katrina, Talmant, Pascaline, Richebourg, Steven, Mugneret, Francine, Tigaud, Isabelle, Mozziconacci, Marie-Joëlle, Laibe, Sophy, Nadal, Nathalie, Terré, Christine, Libouton, Jeanne-Marie, Decottignies, Anabelle, Vikkula, Miikka, and Poirel, Hélène

Abstract

Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis.

Published
2011

46. Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study

Author

UCL, Coyaud, Etienne, Struski, Stephanie, Prade, Nais, Familiades, Julien, Eichner, Ruth, Quelen, Cathy, Bousquet, Marina, Mugneret, Francine, Talmant, Pascaline, Pages, Marie-Pierre, Lefebvre, Christine, Penther, Dominique, Lippert, Eric, Nadal, Nathalie, Taviaux, Sylvie, Poppe, Bruce, Luquet, Isabelle, Baranger, Laurence, Eclache, Virginie, Radford, Isabelle, Barin, Carole, Mozziconacci, Marie-Joëlle, Lafage-Pochitaloff, Marina, Antoine-Poirel, Helene, Charrin, Christiane, Terre, Christine, Brousset, Pierre, Dastugue, Nicole, Broccardo, Cyril, UCL, Coyaud, Etienne, Struski, Stephanie, Prade, Nais, Familiades, Julien, Eichner, Ruth, Quelen, Cathy, Bousquet, Marina, Mugneret, Francine, Talmant, Pascaline, Pages, Marie-Pierre, Lefebvre, Christine, Penther, Dominique, Lippert, Eric, Nadal, Nathalie, Taviaux, Sylvie, Poppe, Bruce, Luquet, Isabelle, Baranger, Laurence, Eclache, Virginie, Radford, Isabelle, Barin, Carole, Mozziconacci, Marie-Joëlle, Lafage-Pochitaloff, Marina, Antoine-Poirel, Helene, Charrin, Christiane, Terre, Christine, Brousset, Pierre, Dastugue, Nicole, and Broccardo, Cyril

Abstract

PAX5 is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). We analyzed 153 adult and child B-ALL harboring karyotypic abnormalities at chromosome 9p, to determine the frequency and the nature of PAX5 alterations. We found PAX5 internal rearrangements in 21% of the cases. To isolate fusion partners, we used classic and innovative techniques (rolling circle amplification-rapid amplification of cDNA ends) and single nucleotide polymorphism-comparative genomic hybridization arrays. Recurrent and novel fusion partners were identified, including NCoR1, DACH2, GOLGA6, and TAOK1 genes showing the high variability of the partners. We noted that half the fusion genes can give rise to truncated PAX5 proteins. Furthermore, malignant cells carrying PAX5 fusion genes displayed a simple karyotype. These data strongly suggest that PAX5 fusion genes are early players in leukemogenesis. In addition, PAX5 deletion was observed in 60% of B-ALL with 9p alterations. Contrary to cases with PAX5 fusions, deletions were associated with complex karyotypes and common recurrent translocations. This supports the hypothesis of the secondary nature of the deletion. Our data shed more light on the high variability of PAX5 alterations in B-ALL. Therefore, it is probable that gene fusions occur early, whereas deletions should be regarded as a late/secondary event. (Blood. 2010;115(15):3089-3097)

Published
2010

47. PRDM16 is frequently rearranged with various partner genes in myeloid malignancies with 1p36 alterations

Author

UCL - SSS/IREC - Institut de recherche expérimentale et clinique, KULeuven - Department of Human Genetics, Institut Paoli-Calmettes - Départements d'Oncologie Moléculaire et de BioPathologie, Hôpital Jeanne de Flandre - Unité Inserm U524, CHU de Nice - Service de Génétique, CHU de Liège - Service de Génétique, UZ Gent - Centrum for Medische Genetica, CHU de Toulouse - Service de Génétique, CHU de Montpellier - Service de Génétique, CHU de Saint-Etienne - Service de Génétique, CHU de Nantes - Service de Génétique, CHU de Bordeaux - Service de Génétique, IPG - Service de Génétique, CHU de Dijon - Service de Génétique, Hôpital de la Pitié-Salpêtrière - Service de Génétique, Institut Gustave Roussy - Service de Génétique, CHU Timone - Laboratoire de Cytogénétique Onco-hématologique, Centre Hospitalier de Versailles - Service de Génétique, Centre Hospitalier de Besançon - Service de Génétique, Centre Hospitalier Lyon Sud - Service de Génétique, CHU de Genève - Service de Génétique, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Wlodarska, Iwona, Mozziconacci, Marie-Joëlle, Roche-Lestienne, Catherine, Raynaud, Sophie, Herens, Christian, Speleman, Frank, Dastugue, Nicole, Taviaux, Sylvie, Nadal, Nathalie, Talmant, Pascaline, Lippert, Eric, Rack, Katrina, Mugneret, Francine, Nguyen-Khac, Florence, Auger, Nathalie, Lafage, Marina, Terré, Christine, Collonge-Rame, Marie-Agnès, Tigaud, Isabelle, Cabrol, Christine, Libouton, Jeanne-Marie, Poirel, Hélène, European Human Genetics Conference, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, KULeuven - Department of Human Genetics, Institut Paoli-Calmettes - Départements d'Oncologie Moléculaire et de BioPathologie, Hôpital Jeanne de Flandre - Unité Inserm U524, CHU de Nice - Service de Génétique, CHU de Liège - Service de Génétique, UZ Gent - Centrum for Medische Genetica, CHU de Toulouse - Service de Génétique, CHU de Montpellier - Service de Génétique, CHU de Saint-Etienne - Service de Génétique, CHU de Nantes - Service de Génétique, CHU de Bordeaux - Service de Génétique, IPG - Service de Génétique, CHU de Dijon - Service de Génétique, Hôpital de la Pitié-Salpêtrière - Service de Génétique, Institut Gustave Roussy - Service de Génétique, CHU Timone - Laboratoire de Cytogénétique Onco-hématologique, Centre Hospitalier de Versailles - Service de Génétique, Centre Hospitalier de Besançon - Service de Génétique, Centre Hospitalier Lyon Sud - Service de Génétique, CHU de Genève - Service de Génétique, Duhoux, François, Ameye, Geneviève, Bahloula, Khadija, Wlodarska, Iwona, Mozziconacci, Marie-Joëlle, Roche-Lestienne, Catherine, Raynaud, Sophie, Herens, Christian, Speleman, Frank, Dastugue, Nicole, Taviaux, Sylvie, Nadal, Nathalie, Talmant, Pascaline, Lippert, Eric, Rack, Katrina, Mugneret, Francine, Nguyen-Khac, Florence, Auger, Nathalie, Lafage, Marina, Terré, Christine, Collonge-Rame, Marie-Agnès, Tigaud, Isabelle, Cabrol, Christine, Libouton, Jeanne-Marie, Poirel, Hélène, and European Human Genetics Conference

Published
2010

48. NOTCH1 Mutations Are Associated With The 14q Deletion In Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)

Author

Nguyen-Khac, Florence, primary, Cosson, Adrien, additional, Chapiro, Elise, additional, Belhouachi, Nabila, additional, Cung, hong-Anh, additional, Keren, Boris, additional, Damm, Frederik, additional, Algrin, Caroline, additional, Lefebvre, Christine, additional, fert-Ferrer, Sandra, additional, Luquet, Isabelle, additional, Gachard, Nathalie, additional, Mugneret, Francine, additional, Terré, Christine, additional, Collonge-Rame, Marie-Agnes, additional, Michaux, Lucienne, additional, Radford-Weiss, Isabelle, additional, Talmant, Pascaline, additional, Veronese, Lauren, additional, Nadal, Nathalie, additional, Struski, Stephanie, additional, Barin, Carole, additional, Helias, Catherine, additional, Lafage, Marina, additional, Lippert, Éric, additional, Auger, Nathalie, additional, Eclache, Virginie, additional, Settegrana, Catherine, additional, Maloum, Karim, additional, Lesty, CLaude, additional, Davi, Frederic, additional, and Merle-Beral, Hélène, additional

Published
2013
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50. Characterization of 14 NUP214-ABL1 fusions in T-cell acute lymphoblastic leukaemia (T-ALL) exhibits a genomic heterogeneity.

Author

UCL - Cliniques universitaires Saint-Luc, UCL, Graux, Carlos, Poirel, Hélène, Lafage, Marina, Dastugue, Nicole, Mugneret, Francine, Berger, Roland, Struski, Stephanie, Gregoire, Marie-Jose, Nadal, Nathalie, Lippert, Eric, Stevens-Kroef, Marian, Cools, Jan, Hagemeijer, Anne, 48th Annual Meeting of the American-Society-of-Hematology, UCL - Cliniques universitaires Saint-Luc, UCL, Graux, Carlos, Poirel, Hélène, Lafage, Marina, Dastugue, Nicole, Mugneret, Francine, Berger, Roland, Struski, Stephanie, Gregoire, Marie-Jose, Nadal, Nathalie, Lippert, Eric, Stevens-Kroef, Marian, Cools, Jan, Hagemeijer, Anne, and 48th Annual Meeting of the American-Society-of-Hematology

Published
2006

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