BCL2 mutations do not confer adverse prognosis in follicular lymphoma patients treated with rituximab

• Published in: American journal of hematology Vol. 92; no. 6; pp. 515 - 519
• Main Authors: Huet, Sarah, Szafer‐Glusman, Edith, Tesson, Bruno, Xerri, Luc, Fairbrother, Wayne J., Mukhyala, Kiran, Bolen, Chris, Punnoose, Elizabeth, Tonon, Laurie, Chassagne‐Clément, Catherine, Feugier, Pierre, Viari, Alain, Jardin, Fabrice, Salles, Gilles, Sujobert, Pierre
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2017; Wiley
• Subjects: Activation-induced cytidine deaminase; Amino acids; Antineoplastic Agents - therapeutic use; Bioinformatics; Computer Science; Cytidine deaminase; Deoxyribonucleic acid; DNA; DNA sequencing; Female; Health risk assessment; Hematology; Humans; Immunotherapy; Life Sciences; Lymphoma; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - genetics; Lymphoma, Follicular - mortality; Male; Medical prognosis; Monoclonal antibodies; Mutation; N-Terminus; Prognosis; Proto-Oncogene Proteins c-bcl-2 - genetics; Rituximab; Rituximab - therapeutic use; Survival; Targeted cancer therapy; Translocation, Genetic; Treatment Outcome
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.24701

BCL2 mutations have been suggested to confer an adverse prognosis to follicular lymphoma (FL) patients, but their prognostic value has not been assessed in patients treated with a rituximab‐containing regimen. Here we evaluated the prognostic value of BCL2 mutations in a large prospective cohort of 252 patients with FL treated with immunochemotherapy in the PRIMA randomized trial. Using a DNA‐targeted sequencing approach, we detected amino acid altering mutations in 135 patients (54%) and showed that these mutations were probably mediated by the over‐activation of AICDA (activation‐induced cytidine deaminase) in the context of the t(14;18) translocation. The BCL2 variants identified in PRIMA patients affected the BH1, BH2, and BH3 functional motifs at a lower frequency than the N‐terminus and flexible loop domain, with mostly conservative aminoacid changes. With a median follow‐up of 6.7 years, we did not observe any impact of BCL2 mutations either on overall survival or progression‐free survival.