JAK2基因突变在急性白血病中的研究进展

Research advances in the role of JAK2 mutations in acute leukemia

摘要:

JAK-STAT 信号通路介导细胞增殖、分化、迁移、凋亡等功能, 该通路与造血系统的发育及一些血液系统疾病的发生密切相关。JAK2-STAT 作为JAK-STAT 通路中的重要信号轴, 它的异常激活在血液系统肿瘤的形成中起重要作用。JAK2V617F 突变是骨髓增殖性疾病发生的重要分子机制, 近年来研究发现在不同类型的急性白血病中JAK2 突变亦有不同的发生率, JAK2 突变可能与急性白血病的发生、治疗及预后密切相关。目前JAK2 突变的致病机制尚未完全阐明, 可能与突变引起JAK-STAT 信号通路的过度活化, 继而导致细胞过度增殖、凋亡分化受阻相关。JAK2 激酶抑制剂也逐渐进入临床试验用于JAK2 突变的血液系统疾病的靶向治疗。该文就近年来JAK2 基因突变与急性白血病的发生、临床特征及其分子靶向治疗等方面的研究进展作一综述。

Abstract:

The Janus kinase -signal transducer and activator of transcription (JAK-STAT) pathway plays pivotal roles in the regulation of cell proliferation, differentiation, migration and apoptosis, which is closely related with the development of hematopoietic cells and some hematological diseases. As an important signaling axis in JAK-STAT pathway, abnormally activated JAK2-STAT signaling is involved in the development of the hematological malignancies. JAK2V617F mutation is the important molecular pathogenesis of myeloproliferative disorders. Recent studies have demonstrated that JAK2 mutations are present in different acute leukemia subtypes and the frequency of mutations is different and that JAK2 mutations might be closely correlated with acute leukemia formation, treatment and prognosis. The pathogenic mechanism of JAK2 mutations has not been completely elucidated. JAK2 mutations might lead to JAK-STAT overactivation, resulting in the excessive proliferation, apoptosis resistance and differentiation blocking of blood cells. JAK2 inhibitors have been rapidly developed as targeted therapies for hematological disorders with JAK2 mutations. This article mainly focuses on recent studies about the role of JAK2 mutations in the pathogenesis, clinical characteristics and targeted therapies of acute leukemia.