Chronic lymphocytic leukemia patients with chromosome 6q deletion as the sole cytogenetic abnormality display a high frequency of RPS15 mutations and have a poor prognosis

Abstract

[EN]Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, with survival times ranging from months to decades, reflecting a great biological diversity. Classical cytogenetical models allow to classify patients in different risk subgroups according to the presence of certain chromosomal aberrations, being the most common the 13q deletion (del(13q)), 17p deletion (del(17p)), 11q deletion (del(11q)), and trisomy 12 (+12).1 By contrast, other less frequent cytogenetic alterations, including 6q deletion (del(6q)), affects a lower but not insignificant percentage of patients (5%). Several studies have suggested an association of del(6q) with inferior outcomes, allocating these CLL cases in an intermediate-risk category,2, 3 although other studies have shown no difference in outcomes.4 The recurrence of del(6q) in other B-cell malignancies strongly suggests that this region contains unidentified tumor-suppressor gene(s). Nevertheless, CLL patients harboring del(6q) remain poorly characterized at the molecular level, partly due to the low incidence of cases, the lack of a FISH-based routinely assessment of del(6q), and the co-occurrence with other abnormalities that masks their clinical and biological significance. Here, we comprehensively characterize for the first time the genetic landscape of CLL patients with del(6q) identified by karyotyping, since we believe that a mutational screening could allow for refinement in predicting overall survival and time to first treatment, as well as provide novel insights into del(6q) CLL pathobiology.