肿瘤细胞治疗研究
英文原题：Advances in the understanding of molecular genetics and therapy of Richter transformation in chronic lymphocytic leukemia.
与基础 CLL/SLL 的克隆相关性见于 80% 的病例，是影响预后的主要因素之一。
Richter转化（RT）是慢性淋巴细胞白血病（CLL）或小淋巴细胞淋巴瘤（SLL）演变为侵袭性淋巴瘤的过程，最常见为弥漫性大B细胞淋巴瘤。RT罕见但侵袭性强，预后差、生存不佳。约80%的病例与基础CLL/SLL存在克隆相关性，这是影响预后的主要因素之一。历史上RT主要采用化学免疫治疗，但TP53、NOTCH1、MYC和CDKN2A等参与细胞存活及增殖的基因频繁突变，使患者对标准治疗产生耐药。近年对RT生物学机制的认识进展，帮助识别出可能由新型选择性药物靶向的遗传及分子病变。通路及免疫检查点抑制剂、双特异性抗体和CAR-T细胞疗法目前均在研究中，并代表有希望的治疗选择。本综述总结当前生物学证据及新型治疗药物的现有数据。
Richter's transformation (RT) is defined as the evolution of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. This complication is rare and aggressive, with poor prognosis and dismal survival. Clonal relationship with the underlying CLL/SLL, observed in 80% of cases, represents one of the main factors affecting prognosis. Treatment has been historically based on chemoimmunotherapy, but frequent mutations in genes involved in cell survival and proliferation-such as TP53, NOTCH1, MYC, CDKN2A-confer resistance to standard treatments. During the last years, advances in the knowledge of the biological mechanisms underlying RT allowed to identify genetic and molecular lesions that can potentially be targeted by novel selective agents. Pathway and checkpoint inhibitors, bispecific antibodies and CAR T-cell therapy are currently under investigation and represent promising treatment options. This review summarizes current biological evidence and available data on novel therapeutic agents.
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