中文摘要：

目的: Histone H2AX 是新奇肿瘤 suppressor，它在 C 终点(Ser139 和 Tyr142 ) 的 phosphorylation 为肿瘤房间 apoptosis 被要求。现在的学习的目的是阐明在 vitro 在长期的骨髓内产生的白血病房间位于 H2AX 的导致 imatinib 的 C 终端 phosphorylation 下面的机制。

英文摘要：

Aim： Histone H2AX is a novel tumor suppressor and its phosphorylation at the C terminus （Ser139 and Tyr142） is required for tumor cell apoptosis. The aim of the present study was to elucidate the mechanisms underlying imatinib-induced C-terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro. Methods： BCR-ABL-positive K562 cells were used. Microscopy, Western blotting and flow cytometry were used to study the signaling pathways that regulate imatinib-induced H2AX phosphorylation and the apoptotic mechanisms. Results： Treatment of K562 cells with imatinib （1-8 μmol/L） induced phosphorylation of H2AX at Ser139 and Tyr142 in time- and dose-dependent manners. In contrast, imatinib at the same concentrations did not affect H2AX acetylation at Lys 5, and the acetylated H2AX maintained a higher level in the cells. Meanwhile, imatinib （1-8 μmol/L） activated caspase-3 and its downstream mammalian STE20-like kinase 1 （Mst1）, and induced apoptosis of K562 cells. The caspase-3 inhibitor Z-VAD （40 μmol/L） reduced imatinibinduced H2AX phosphorylation at Ser139 and Tyr142 and blocked imatinib-induced apoptosis of K562 cells. Imatinib （4 pmol/L） induced expression of Williams-Beuren syndrome transcription factor （WSTF）, but not wild-type p53-induced phosphatase 1 （Wipl） in K562 cells. Conclusion： The caspase-3/Mstl pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib.