布鲁顿酪氨酸激酶（Btk）是BCR信号传导通路中重要的下游分子，调节B细胞的增殖、分化和凋亡，Btk信号通路的持续活化可能参与了B细胞非霍奇金淋巴瘤（B-NHL）的发生。针对该靶点所开发的抑制剂PCI-32765在某些类型B-NHL中已显示出较好疗效。但是不同B-NHL肿瘤组织中Btk表达量、活化状态以及诱导其持续活化的原因尚不十分明确，与其他抗淋巴瘤靶向药物先明确机制再研发药物的过程不同，PCI-32765的详细抗淋巴瘤机制还有待探讨。我们前期研究发现不同类型B-NHL均存在Btk过量表达和持续活化，且可能与Btk[457]基因多态性密切相关。体外研究还提示PCI-32765可通过降低Btk、PLCγ2和ERK的磷酸化水平来抑制JVM2淋巴瘤细胞系增殖。本研究拟进一步在临床病例中验证该结果，有望丰富Btk作为B-NHL临床治疗靶点的理论依据，并为第二代Btk抑制剂研发提供基础数据。

The Bruton's tyrosine kinase (Btk) pathway is a downstream mediator of the B-cell receptor (BCR) pathway, which is crucial in B-cell production and maintenance, and a potential therapeutic target. The constitutive activation of this pathway plays a significant role in proliferation and survival in B-cell NHL. The Btk PCI-32765 already showed its potential anti-tumor ability toward B-NHL in vitro and in clinical trials. But the different status and reason for this constitutively activation of Btk in different subtypes of B-NHL, detailed anti-tumor mechanisms of PCI-32765 is still unknown. In our fundamental experiment we found that Btk gene the 457th nucleotide showed the single nucleotide polymorphism (SNP) loci, may induce the constitutively activated Btk in B-NHL. Furthermore, PCI-32765 could inhibit proliferation of JVM2 cell lines through suppression of phosphorylation of Btk, PLCγ2 and ERK. Totally, PCI-32765 is potential new target cancer therapy for the treatment of B-NHL.