KT是骨髓增殖性肿瘤的治疗靶点

Objective: To study the therapeutic effect of AKT inhibitor on the proliferation of bone marrow tumor. Methods: the W515L MPN expression was induced by retroviral infection to construct the MPL cell model. The component activation of the signal pathway was detected by Western blot assay. Cells were treated by AKT inhibitor and the proliferation of MPN cells were detected by cell counting method and clone formation unit test. AnnexinV staining was used to detect cell apoptosis, and the cell cycle was detected by BrdU method. The animal survival experiment was performed to analyze the effect of AKT inhibitor on the survival rate of MPN mouse model . Results: the overexpression of MPLW515L could significantly activate PI3K/AKT, JAK/STAT and other signaling pathways. Blocking those signal pathways can inhibit the proliferation and promote the apoptosis of MPN cell model. Among them, the PI3K/AKT inhibitor had the most significant effect, and the proportion of G1ME cells in the mitotic phase S was decreased, while the proportion of G1/G0 phase was increased, the cell cycle arrest function was shown. At the same time, in the blood samples of patients with MPN, blocking PI3K/AKT can also inhibit the colony forming units of bone marrow progenitor cells, and significantly increase the survival rate of animal model. Conclusion: AKT is a target for the treatment of bone marrow proliferative tumors