Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH.
Semin Hematol. 2014 Jul;51(3):206-18. doi: 10.1053/j.seminhematol.2014.05.007. Epub 2014 May 15.
The pathogenesis and progression of normal B-cell development to malignant transformation of chronic lymphocytic leukemia (CLL) is still poorly understood and has hampered attempts to develop targeted therapeutics for this disease. The dependence of CLL cells on B-cell receptor signaling has fostered a new area of basic and therapeutic research interest. In particular, identification of the dependence of CLL cells on both phosphatidylinositol 3-kinase delta and Bruton's tyrosine kinase signaling for survival and proliferation has come forth through well-performed preclinical studies and subsequent trials demonstrating dramatic efficacy. This review outlines essential components of B-cell receptor signaling and briefly addresses therapeutics that are emerging to target these in patients with CLL and related lymphoid malignancies.
慢性淋巴细胞白血病（CLL）正常 B 细胞发育为恶性转化的发病机制和进展仍知之甚少，这阻碍了针对这种疾病开发靶向治疗的尝试。CLL 细胞对 B 细胞受体信号的依赖性促进了基础和治疗研究的一个新领域。特别是，通过进行良好的临床前研究和随后的试验证明了显著的疗效，鉴定出 CLL 细胞对磷脂酰肌醇 3-激酶 δ和布鲁顿酪氨酸激酶信号的依赖性对于存活和增殖。这篇综述概述了 B 细胞受体信号的基本组成部分，并简要介绍了针对 CLL 和相关淋巴恶性肿瘤患者的这些靶点出现的治疗方法。
