1. Gain of the short arm of chromosome 2 (2p gain) has a significant role in drug‐resistant chronic lymphocytic leukemia
- Author
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Kostopoulou, Fotini, Gabillaud, Clementine, Chapiro, Elise, Grange, Beatrice, Tran, Julie, Bouzy, Simon, Degaud, Michael, Ghamlouch, Hussein, Le Garff‐Tavernier, Magali, Maloum, Karim, Choquet, Sylvain, Leblond, Veronique, Gabarre, Jean, Lavaud, Anne, Morel, Veronique, Roos‐Weil, Damien, Uzunov, Madalina, Guieze, Romain, Bernard, Olivier A., Susin, Santos A., Tournilhac, Olivier, Nguyen‐Khac, Florence, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), 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)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut Gustave Roussy (IGR), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École pratique des hautes études (EPHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
- Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology ,Adult ,Male ,Immunoglobulin Variable Region ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Polymorphism, Single Nucleotide ,Immunophenotyping ,Time-to-Treatment ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Recurrence ,immune system diseases ,hemic and lymphatic diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Antineoplastic Combined Chemotherapy Protocols ,Chromosome Duplication ,Humans ,Longitudinal Studies ,Protein Kinase Inhibitors ,In Situ Hybridization, Fluorescence ,Original Research ,Cancer Biology ,Aged ,Chromosome Aberrations ,drug resistance ,2p gain ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Middle Aged ,Prognosis ,Leukemia, Lymphocytic, Chronic, B-Cell ,Treatment Outcome ,Drug Resistance, Neoplasm ,Chromosomes, Human, Pair 2 ,Karyotyping ,Mutation ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,chronic lymphocytic leukemia ,Female - Abstract
International audience; The different types of drug resistance encountered in chronic lymphocytic leukemia (CLL) cannot be fully accounted for by the 17p deletion (and/or TP53 mutation), a complex karyotype (CK), immunoglobulin heavy-chain variable region genes (IGHV) status and gene mutations. Hence, we sought to assess the associations between recurrent genomic abnormalities in CLL and the disease's development and outcome. To this end, we analyzed 64 samples from patients with CLL and gain of the short arm of chromosome 2 (2p+), which is frequent in late-stage and relapsed/refractory CLL. We found that fludarabine/cyclophosphamide/rituximab (a common first-line treatment in CLL) is not effective in removing the 2p+ clone - even in samples lacking a CK, the 17p deletion or unmutated IGHV. Our results suggest strongly that patients with CLL should be screened for 2p+ (using karyotyping and fluorescence in situ hybridization) before a treatment option is chosen. Longer follow-up is now required to evaluate bendamustine-rituximab, ibrutinib, and idelalisib-rituximab treatments.
- Published
- 2019