慢性淋巴细胞白血病靶向治疗的研究进展

doi:10.3969/j.issn.1674-8115.2024.02.013

摘要/Abstract

摘要：

慢性淋巴细胞白血病（chronic lymphocytic leukemia，CLL）是小B细胞淋巴瘤和白血病的一种，也是B细胞克隆增殖性肿瘤。该病具有明显的异质性，大多数患者的病程趋于惰性，但目前仍不可治愈。异常的信号转导机制是CLL发病机制中不可或缺的。在CLL中，常见的异常信号通路包括B细胞受体信号、细胞凋亡、核因子κB（nuclear factor kappa-B，NF-κB）信号以及Notch信号通路等。针对这些信号通路，研发了一系列的靶向药物，如布鲁顿酪氨酸激酶抑制剂（伊布替尼、泽布替尼）、磷酸化磷脂酰肌醇3激酶抑制剂（杜韦利西布）、B细胞淋巴瘤2抑制剂（维奈克拉）等，在临床上显著改变了患者的预后。其他靶向药物如fenebrutinib、nemtabrutinib、厄布利塞等，还有免疫肿瘤学和T细胞工程领域发展的嵌合抗原受体T细胞疗法，目前尚在临床试验阶段。更加个体化的治疗方式正在探索，未来可能成为潜在的治疗选择。该文对CLL领域的相关文献进行梳理，就CLL分子机制及靶向治疗的最新研究进行综述。

关键词: 慢性淋巴细胞白血病, 分子机制, 靶向治疗, 嵌合抗原受体T细胞治疗

Abstract:

Chronic lymphocytic leukemia (CLL) is one of small B-cell lymphomas and leukemias, characterized as a clonal disease of mature B cells. The disease is remarkably heterogeneous, with the majority of patients having an indolent course, yet they are currently incurable. Abnormal signaling pathways are indispensable in the pathogenesis of CLL. In CLL, the common abnormalities of signaling pathways include B-cell receptor (BCR) signaling, apoptosis, nuclear factor kappa B (NF-κB) signaling and Notch signaling. According to the target in signaling pathways, a series of targeted drugs, such as Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, zanubrutinib), phosphorylate phosphoinositide 3-kinase (PI3K) inhibitor (duvelisib) and B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax), which have significantly changed the prognosis of patients in clinic. Other targeted drugs, such as fenebrutinib, nemtabrutinib and umbralisib, as well as chimeric antigen receptor T-cell (CAR-T) therapy developed in the field of immuno-oncology and T cell engineering, are currently under trial, with more personalized treatment modalities being explored, which may become potential drug targets in the future. In this paper, relevant literature of CLL was reviewed, and recent research progress in molecular pathogenesis and targeted therapies of chronic lymphocytic leukemia was reviewed.

Key words: chronic lymphocytic leukemia (CLL), molecular pathogenesis, targeted therapy, chimeric antigen receptor T-cell (CAR-T) therapy

中图分类号:

R557.4

丁艳玲, 李杰, 袁军, 李燕. 慢性淋巴细胞白血病靶向治疗的研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(2): 264-270.

DING Yanling, LI Jie, YUAN Jun, LI Yan. Research progress in targeted therapies of chronic lymphocytic leukemia[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(2): 264-270.

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