학술논문
Gain of the short arm of chromosome 2 (2p gain) has a significant role in drug‐resistant chronic lymphocytic leukemia
Document Type
article
Author
Fotini Kostopoulou; Clementine Gabillaud; Elise Chapiro; Beatrice Grange; Julie Tran; Simon Bouzy; Michael Degaud; Hussein Ghamlouch; Magali Le Garff‐Tavernier; Karim Maloum; Sylvain Choquet; Veronique Leblond; Jean Gabarre; Anne Lavaud; Veronique Morel; Damien Roos‐Weil; Madalina Uzunov; Romain Guieze; Olivier A. Bernard; Santos A. Susin; Olivier Tournilhac; Florence Nguyen‐Khac; the French Innovative Leukemia Organization (FILO) group
Source
Cancer Medicine, Vol 8, Iss 6, Pp 3131-3141 (2019)
Subject
Language
English
ISSN
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.