The effect of the JAK2 inhibitor TG101209 against T cell acute lymphoblastic leukemia (T-ALL) is mediated by inhibition of JAK-STAT signaling and activation of the crosstalk between apoptosis and autophagy signaling
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Zhao Cheng1, Yifang Yi1, Sisi Xie1, Haizhi Yu1, Hongling Peng1 and Guangsen Zhang1
1Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
Hongling Peng, email: [email protected]om
Keywords: T-ALL, apoptosis, autophagy, JAK -STAT
Received: March 22, 2017 Accepted: September 23, 2017 Published: October 23, 2017
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.
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