Aberrant signal transduction through the B cell receptor (BCR) plays a critical role in the pathogenesis of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). BCR-dependent signaling is necessary for the growth and survival of neoplastic cells, making inhibition of down-stream pathways a logical therapeutic strategy. Indeed, selective inhibitors against Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) have been shown to induce high rates of response in CLL and other B cell lymphomas. In particular, the development of BTK inhibitors revolutionized the treatment approach to CLL, demonstrating long-term efficacy. While BTK inhibitors are widely used for multiple lines of treatment, PI3K inhibitors are much less commonly utilized, mainly due to toxicities. CLL remains an incurable disease and effective treatment options after relapse or development of TKI resistance are greatly needed. This review provides an overview of BCR signaling, a summary of the current therapeutic landscape, and a discussion of the ongoing trials targeting BCR-associated kinases.

中文翻译：

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靶向慢性淋巴细胞白血病中的 B 细胞受体信号通路


B 细胞受体 (BCR) 的异常信号转导在慢性淋巴细胞白血病 (CLL)/小淋巴细胞淋巴瘤 (SLL) 的发病机制中起着至关重要的作用。 BCR 依赖性信号传导对于肿瘤细胞的生长和存活是必要的，这使得抑制下游通路成为一种合理的治疗策略。事实上，针对布鲁顿酪氨酸激酶 (BTK) 和磷酸肌醇 3-激酶 (PI3K) 的选择性抑制剂已被证明可在 CLL 和其他 B 细胞淋巴瘤中诱导高反应率。特别是，BTK 抑制剂的开发彻底改变了 CLL 的治疗方法，显示出长期疗效。虽然 BTK 抑制剂广泛用于多种治疗，但 PI3K 抑制剂的使用要少得多，主要是由于毒性。 CLL 仍然是一种无法治愈的疾病，在复发或出现 TKI 耐药性后，非常需要有效的治疗方案。本综述提供了 BCR 信号传导的概述、当前治疗前景的总结以及针对 BCR 相关激酶正在进行的试验的讨论。