T细胞急性淋巴细胞白血病（T-ALL）是一种具有高度侵袭性的恶性血液肿瘤，对糖皮质激素及化疗耐药是该病治疗的主要瓶颈。耐药T-ALL存在JAKs/STATs信号转导紊乱及JAKs基因变异或异常表达。T-ALL耐药与增强的细胞“自噬”及“凋亡”耐受相关。本项目拟用JAK2特异抑制剂—TG101209干预耐药T-ALL细胞株及原代耐药T-ALL细胞及C-MYC过表达的T-ALL斑马鱼模型，观察药物的抗T-ALL活性及耐药逆转效应。并围绕药物作用前后所涉及的“JAKs/STATs”信号途径及“上/下游调控元件”进行调控机制研究，澄清药物干预下耐药细胞”自噬增强/凋亡耐受”转换的亚细胞变化模型及相关靶分子变化规律，为耐药T-ALL治疗探索新的分子靶向治疗途径。

T cell acute lymphoblastic leukemia (T-ALL) is a high progressive hematological malignances and Glucocorticosteroid hormones resistance is the major “bottleneck” of T-ALL therapy. Resistant T-ALL presents JAKs/STATs signal transduction abnormal and JAKs variation. T-ALL resistance is related with enhanced “Autophage” and “Apoptosis” resistance. Our project plans to use specific JAK2 inhibitor –TG101209 intervene resistant T-ALL cell lines, primary T-ALL cells and C-MYC induced transgenic zebrafish model, and investigate the anti-leukemic effect. Meanwhile, we will further study the mechanism of “JAKs/STATs” signal pathway and its target “element” regulation. Clarifying the “Autophage enhancement/Apoptosis resistance” transition subcellular structure model and related factor regulation under TG101209 treatment in resistant T-ALL cells,provid a novel therapeutic approach to T-ALL treatment.