Parikh Sameer A, Shanafelt Tait D
Division of Hematology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Curr Hematol Malig Rep. 2014 Sep;9(3):294-9. doi: 10.1007/s11899-014-0223-4.
Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) to a more aggressive B-cell lymphoma, most commonly diffuse large B-cell lymphoma. Approximately 5-10% of CLL patients develop this complication during long-term follow-up. Traditional risk factors for future RS include clinical (advanced Rai stage), biological (ZAP-70, CD38, CD49d) and genetic (del17p, del11q) characteristics at the time of CLL diagnosis. The impact of CLL therapy (purine-nucleoside analogue and/or alkylator-based chemoimmunotherapy and kinase inhibitor therapy) on the risk of RS remains controversial. Both heritable (germline) and acquired (somatic) genetic mutations contribute to risk of RS. Germline polymorphisms in genes related to CD38, LRF4, and BCL-2 have been implicated in the development of RS. Somatic mutations contributing to the development of RS include TP53 disruption, c-myc activation, CDKN2A loss and NOTCH1 mutations. This review summarizes recent advances in our understanding of the biological and genetic factors contributing to RS in CLL patients.
里氏综合征（RS）被定义为慢性淋巴细胞白血病（CLL）转化为侵袭性更强的B细胞淋巴瘤，最常见的是弥漫性大B细胞淋巴瘤。约5%-10%的CLL患者在长期随访中会出现这种并发症。CLL未来发生RS的传统风险因素包括CLL诊断时的临床特征（Rai分期晚期）、生物学特征（ZAP-70、CD38、CD49d）和遗传学特征（17p缺失、11q缺失）。CLL治疗（嘌呤核苷类似物和/或基于烷化剂的化疗免疫疗法以及激酶抑制剂疗法）对RS风险的影响仍存在争议。遗传性（种系）和获得性（体细胞）基因突变均会增加RS风险。与CD38、LRF4和BCL-2相关的基因种系多态性与RS的发生有关。导致RS发生的体细胞突变包括TP53破坏、c-myc激活、CDKN2A缺失和NOTCH1突变。本综述总结了我们对CLL患者发生RS的生物学和遗传因素理解的最新进展。
