Cheng Zhao, Yi Yifang, Xie Sisi, Yu Haizhi, Peng Hongling, Zhang Guangsen
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Oncotarget. 2017 Oct 23;8(63):106753-106763. doi: 10.18632/oncotarget.22053. eCollection 2017 Dec 5.
Previous reports have shown that active JAK2 contributes to T cell acute lymphoblastic leukaemia (T-ALL) development and that JAK inhibitors may be a potential treatment for T-ALL. In the current study, the JAK2 inhibitor TG101209 was used to treat T-ALL cell lines and primary T-ALL cells. The effects of TG101209 on T-ALL cells were determined, and the signaling proteins related to cell growth, apoptosis and autophagy were analysed. The results indicated that TG101209 significantly inhibited T-ALL cell proliferation and induced cell apoptosis in a dose-dependent manner. The mechanisms involved the suppression of the JAK2-STAT signaling pathway and activation of apoptosis or autophagy. Additionally, a JAK2 gene copy gain (FISH) and up-regulated JAK2, LC3 and Beclin1 expression (western blotting) were observed in T-ALL samples compared with healthy controls, which implied that JAK2 is a target for T-ALL treatment. TG101209 initiated apoptosis and autophagy in T-ALL cells; therefore, this JAK2 inhibitor may be a potential drug or alternative therapy for T-ALL.
先前的报告表明，活性JAK2有助于T细胞急性淋巴细胞白血病（T-ALL）的发展，并且JAK抑制剂可能是T-ALL的一种潜在治疗方法。在当前研究中，JAK2抑制剂TG101209被用于治疗T-ALL细胞系和原发性T-ALL细胞。测定了TG101209对T-ALL细胞的影响，并分析了与细胞生长、凋亡和自噬相关的信号蛋白。结果表明，TG101209以剂量依赖的方式显著抑制T-ALL细胞增殖并诱导细胞凋亡。其机制涉及抑制JAK2-STAT信号通路以及激活凋亡或自噬。此外，与健康对照相比，在T-ALL样本中观察到JAK2基因拷贝数增加（荧光原位杂交）以及JAK2、LC3和Beclin1表达上调（蛋白质免疫印迹法），这意味着JAK2是T-ALL治疗的一个靶点。TG101209引发T-ALL细胞凋亡和自噬；因此，这种JAK2抑制剂可能是T-ALL的一种潜在药物或替代疗法。
