Gain of the short arm of chromosome 2 (2p gain) has a significant role in drug‐resistant chronic lymphocytic leukemia. (7th May 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Cancer medicine. Volume 8:Number 6(2019:Jun.)
• Page Start: 3131
• Page End: 3141
• Publication Date: 2019-05-07
• Subjects: 2p gain -- chronic lymphocytic leukemia -- drug resistance; 616.994005
• DOI: 10.1002/cam4.2123
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: 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. Abstract : We report on a series of 64 chronic lymphocytic leukemia (CLL) patients harboring a 2p gain. To the best of our knowledge, this is the largest yet studied cohort of patients with 2p+ CLL. We performed a detailed longitudinal analysis of samples collected before and after standard CLL treatments.