Genomic mutation profile in progressive chronic lymphocytic leukemia patients prior to first-line chemoimmunotherapy with FCR and rituximab maintenance (REM)

Abstract

Chronic Lymphocytic Leukemia (CLL) is the most prevalent leukemia in Western countries and is notable for its variable clinical course. This variability is partly reflected by the mutational status of IGHV genes. Many CLL samples have been studied in recent years by next-generation sequencing. These studies have identified recurrent somatic mutations in NOTCH1, SF3B1, ATM, TP53, BIRC3 and others genes that play roles in cell cycle, DNA repair, RNA metabolism and splicing. In this study, we have taken a deep-targeted massive sequencing approach to analyze the impact of mutations in the most frequently mutated genes in patients with CLL enrolled in the REM (rituximab en mantenimiento) clinical trial. The mutational status of our patients with CLL, except for the TP53 gene, does not seem to affect the good results obtained with maintenance therapy with rituximab after front-line FCR treatment.

Fig 1. Incidence and distribution of mutations in the 26 analyzed genes and genetic markers in the REM cohort.

Rows correspond to sequenced genes and genetic features; columns represent individual patients with CLL. (Figure done with oncoprint tool in cBioPortal). Colour code: IGHV: red, unmutated IGHV, blue: mutated IGHV, orange: no data. Genetic alterations: green, missense mutation; black, truncating mutation; light blue, deletion; red, gain.