Tadmor Tamar, Levy Ilana
Hematology Unit, Bnai-Zion Medical Center, Haifa 3339419, Israel.
The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3525422, Israel.
Cancers (Basel). 2021 Oct 14;13(20):5141. doi: 10.3390/cancers13205141.
Richter transformation (RT) is a poorly understood complication of chronic lymphocytic leukemia (CLL) with a dismal prognosis. It is associated with a switch in histopathology and biology, generally with a transformation of the original CLL clone to diffuse large B-cell lymphoma (DLBCL) or less frequently to Hodgkin's variant of Richter transformation (HVRT). It occurs in 2-10% of CLL patients, with an incidence rate of 0.5-1% per year, and may develop in treatment-naïve patients, although it is more common following therapy. In recent years, there has been a deeper understanding of the molecular pathogenesis of RT that involves the inactivation of the TP53 tumor suppressor gene in 50-60% of cases and the activation of aberrations of NOTCH1 and MYC pathways in about 30% of cases. Compared to the preceding CLL, 80% of cases with DLBCL-RT and 30% of HVRT harbor the same IGHV-D-J rearrangements, indicating a clonal evolution of the disease, while the remaining cases represent de novo lymphomas that are clonally unrelated. Despite advances in understanding the molecular variations and the pathogenesis of the disease, there is still no significant improvement in patient outcomes. However, if no clinical trials were designed for patients with RT in the past, now there many studies for these patients that incorporate new drugs and novel combinations that are being explored. In this review, we summarize the new information accumulated on RT with special emphasis on results involving the novel therapy tested for this entity, which represents an unmet clinical need.
里氏转化（RT）是慢性淋巴细胞白血病（CLL）一种了解甚少的并发症，预后不佳。它与组织病理学和生物学的转变相关，通常是原始CLL克隆转变为弥漫性大B细胞淋巴瘤（DLBCL），或较少见地转变为里氏转化的霍奇金变异型（HVRT）。它发生在2%-10%的CLL患者中，年发病率为0.5%-1%，可在未经治疗的患者中发生，尽管在治疗后更常见。近年来，对RT的分子发病机制有了更深入的了解，在50%-60%的病例中涉及TP53肿瘤抑制基因的失活，在约30%的病例中涉及NOTCH1和MYC通路畸变的激活。与之前的CLL相比，80%的DLBCL-RT病例和30%的HVRT病例具有相同的IGHV-D-J重排，表明疾病的克隆进化，而其余病例代表克隆无关的新发淋巴瘤。尽管在了解疾病的分子变异和发病机制方面取得了进展，但患者的预后仍没有显著改善。然而，如果过去没有为RT患者设计临床试验，现在有许多针对这些患者的研究正在探索新药和新组合。在这篇综述中，我们总结了关于RT积累的新信息，特别强调涉及针对该实体测试的新疗法的结果，这代表了未满足的临床需求。
