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

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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

Edité par CCSD ; Wiley -

International audience. 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.

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