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[JAK2/STAT信号通路抑制剂与血液系统恶性肿瘤——综述]

[Inhibitors of JAK2/STAT Signaling Pathway and Hematologic Malignancies-Review].

作者信息

Zhao Ya-Ling, Liu Gui-Min, Zhang Li-Jun, Liang Wen-Tong, Cheng Zhi-Yong

机构信息

Department of Hematology, Baoding Municipal First Hospital, Baoding 071000, Hebei Province, China; Department of Medical Dingzhou People's Hospital, Dingzhou 073000, Hebei Province, China.

Department of Hematology, Baoding Municipal First Hospital, Baoding 071000, Hebei Province, China; Chengde Medical College, Chengde 067000, Hebei Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Aug;24(4):1275-9. doi: 10.7534/j.issn.1009-2137.2016.04.059.

Abstract

Jauns kinase (JAK)/transducer and activator of transcription(STAT) pathway is a classical approach to study the rapid changes of the gene expression in specific target cells by a variety of extracellular signals. The JAK and STAT transfer cytokine receptor signaling plays a unique role in multiple cellular and molecular biological changes.The abnormal signal of JAK/STAT pathway will lead to the hematopoietic abnormalities.Studies had shown that the abnormal activation of JAK2/STAT signaling pathway are in many kinds of malignant hematological diseases, such as in acute lymphoblastic/myeloid leukemia, chronic myeloid leukemia, lymphoma, myelodysplastic syndromes, myeloprofilerative neoplasm, especially in the patients of myeloproliferative neoplasm(MPN) with JAK gene mutation(JAK2V617F), this mutation has an important value for MPN diagnosis. At present, the effect of the specific inhibitors of JAK2 has showed good perspective, which had been applied to clinic treatment and achieved remarkable curative effect. In this review, the JAK2/STAT signaling transduction, the JAK2 signal and hematologic malignancies, the kagulation of signaling pathway and the inhibitors of JAK2/STAT signaling pathway are summarized.

摘要

Janus激酶(JAK)/信号转导子和转录激活子(STAT)途径是研究多种细胞外信号导致特定靶细胞基因表达快速变化的经典方法。JAK和STAT传递细胞因子受体信号在多种细胞和分子生物学变化中发挥独特作用。JAK/STAT途径的异常信号会导致造血异常。研究表明,JAK2/STAT信号通路的异常激活存在于多种恶性血液疾病中,如急性淋巴细胞/髓细胞白血病、慢性髓细胞白血病、淋巴瘤、骨髓增生异常综合征、骨髓增殖性肿瘤,尤其是在伴有JAK基因突变(JAK2V617F)的骨髓增殖性肿瘤(MPN)患者中,这种突变对MPN诊断具有重要价值。目前,JAK2特异性抑制剂的效果已显示出良好前景,已应用于临床治疗并取得显著疗效。本文综述了JAK2/STAT信号转导、JAK2信号与血液系统恶性肿瘤、信号通路的调控以及JAK2/STAT信号通路抑制剂。

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