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

PLoS One. 2021 Sep 10;16(9):e0257353. doi: 10.1371/journal.pone.0257353. eCollection 2021.


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.

Grant support

This work was supported by the Instituto de Salud Carlos III (ISCII) of the Spanish Ministry of Economy and Competence (MINECO) ISCIII-MINECO AES-FEDER (Plan Estatal de I+D+I 2008-2011 and 2013-2016 (MSB: RD12/0036/0060, PI14/00221, PIE14/0064, PI17/00272; MSB and JGR: CIBERONC CB16/12/00291, MA and MG: CB16/12/00233), Comunidad Autónoma de Madrid ( (MSB: B2017/BMD3778), MSB: Fundación de la Asociación Española Contra el Cáncer ( and JAGM: Roche Farma, S.A., Madrid, Spain. JGR was a recipient of an iPFIS predoctoral fellowship (IFI14/00003) and MSB held a Miguel Servet II contract (CPII16/00024), supported by ISCIII-MINECO AES-FEDER (Plan Estatal I+D+I 2013-2016) and the Fundación de Investigación Biomédica Puerta de Hierro. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.