Feng Gege, Wang Xin
Department of Hematology, Provincial Hospital Affiliated to Shandong University , Jinan, Shandong , P. R. China.
Leuk Lymphoma. 2014 Dec;55(12):2699-705. doi: 10.3109/10428194.2014.891026. Epub 2014 Mar 18.
The antigen-dependent B-cell receptor (BCR) is triggered by binding to external antigens and transmits signals in normal B lymphocytes. Tonic signaling through the BCR plays a crucial role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). Spleen tyrosine kinase (Syk) is a key component of both BCR signals, and regulates multiple physiological functions of B lymphocytes. Studies have defined enhanced gene expression and protein expression of Syk in CLL cells which are closely related to the status of the immunoglobulin heavy chain variable region genes (IgVH). Recently, abrogating the BCR-induced signaling pathway by Syk inhibitors has represented a novel and active therapeutic approach for CLL. Studies of the correlation between Syk and ZAP-70 expression in CLL cells have brought a new perspective to determining the value of Syk in evaluating the effect of therapy and the prognosis of CLL. Therefore, we here review the role of Syk in the pathogenesis of CLL and provide an update of progress in the clinical development of Syk inhibitors.
抗原依赖性B细胞受体（BCR）通过与外部抗原结合而被触发，并在正常B淋巴细胞中传递信号。通过BCR的张力信号传导在慢性淋巴细胞白血病（CLL）的发病机制和进展中起关键作用。脾酪氨酸激酶（Syk）是两种BCR信号的关键组成部分，并调节B淋巴细胞的多种生理功能。研究已确定CLL细胞中Syk的基因表达和蛋白表达增强，这与免疫球蛋白重链可变区基因（IgVH）的状态密切相关。最近，通过Syk抑制剂消除BCR诱导的信号通路已成为一种针对CLL的新型有效治疗方法。对CLL细胞中Syk与ZAP-70表达之间相关性的研究为确定Syk在评估CLL治疗效果和预后中的价值带来了新的视角。因此，我们在此综述Syk在CLL发病机制中的作用，并提供Syk抑制剂临床开发进展的最新情况。
