Institute of Hematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, China.
Exp Hematol Oncol. 2014 Jan 28;3(1):4. doi: 10.1186/2162-3619-3-4.
Research over the role of Bruton's agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223. This review discussed in details the role of BTK in B-cell signaling, molecular interactions between B cell lymphoma/leukemia cells and their microenvironment. Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized.
对布鲁顿氏酪氨酸激酶（BTK）在 B 淋巴细胞发育、分化、信号转导和存活中的作用的研究，使人们更好地了解了 B 细胞恶性肿瘤的发病机制。BTK 活性的下调是治疗 B 细胞恶性肿瘤患者的一种有吸引力的新策略。伊布替尼（PCI-32765）是一种有效的 BTK 抑制剂，通过与 BTK 活性位点（TH/SH1 结构域）中的半胱氨酸 481 不可逆结合，并抑制 BTK 上 Tyr223 的磷酸化，从而在 B 细胞恶性肿瘤中诱导显著的反应。本文详细讨论了 BTK 在 B 细胞信号转导中的作用，以及 B 细胞淋巴瘤/白血病细胞与其微环境之间的分子相互作用。总结了新型 BTK 抑制剂伊布替尼（PCI-32765）在 B 细胞恶性肿瘤中的临床试验。
