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.
Highlights
Chronic lymphocytic leukemia (CLL, the most common lymphoproliferative disorder among elderly adults in Western countries) is characterized by the progressive accumulation of mature CD5+ B lymphocytes in the bone marrow, peripheral blood, and secondary lymphoid organs
To exclude variations related to the technical limitations of Fluorescence in situ hybridization (FISH), we considered that a difference of more than 20% in the number of 2p+ cells was a marked change between pretreatment and relapse, except when a clone was no longer detected or when we were able to perform a valid comparison with other clones
We corroborated our previous report whereby 2p gain is frequent in untreated, late-stage chronic lymphocytic leukemia (CLL) (32 of the 36 cases [89%] of Binet stage B/C CLL in the present cohort) and in relapsed/refractory CLL (22% of the Bendamustine/ofatumumab and methylprednisolone (BOMP) trial, unpublished data).[12,13]
Summary
GEFLUC, Grant/Award Number: 2017; CURAMUS, Grant/Award Number: INCADGOS-Inserm_12560; Association Laurette Fugain, Grant/Award Number: ALF 14/08; Fondation ARC pour la Recherche sur le Cancer, Grant/Award Number: SFI20111203530; Roche Diagnostics, Grant/Award Number: 2017
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