Service d'hématologie biologique, Hospices Civils de Lyon, 69495, Pierre Bénite cedex, France.
INSERM1052, CNRS 5286, Université Claude Bernard, Faculté de Médecine Lyon-Sud Charles Mérieux, Université de Lyon, 69495, Pierre Bénite cedex, France.
Am J Hematol. 2017 Jun;92(6):515-519. doi: 10.1002/ajh.24701. Epub 2017 Mar 24.
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.
BCL2 突变被认为与滤泡性淋巴瘤（FL）患者的不良预后相关，但在接受含利妥昔单抗方案治疗的患者中，其预后价值尚未得到评估。在这里，我们在 PRIMA 随机试验中评估了 252 例接受免疫化疗治疗的 FL 患者的大前瞻性队列中 BCL2 突变的预后价值。使用靶向 DNA 的测序方法，我们在 135 例患者（54%）中检测到氨基酸改变的突变，并表明这些突变可能是在 t（14；18）易位的背景下，AICDA（激活诱导的胞嘧啶脱氨酶）的过度激活介导的。在 PRIMA 患者中鉴定的 BCL2 变体在 BH1、BH2 和 BH3 功能基序中的频率低于 N 末端和柔性环结构域，主要是保守的氨基酸变化。在中位随访 6.7 年的时间里，我们没有观察到 BCL2 突变对总生存期或无进展生存期有任何影响。
