OBJECTIVETo study the therapeutic effect of AKT inhibitor on the myeloproliferative neoplasms(MPN) and its significanse.

METHODSThe MPL W515L expression was induced by retroviral infection to construct the MPN cell model. The constitutive 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. Annexin V 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.

RESULTSThe overexpression of MPL W515L could significantly activate PI3K/AKT, JAK/STAT and other signaling pathways. Blocking these signal pathways could 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 decreased, while the proportion of G/Gphase increased, the cell cycle arrest function was shown. At the same time, in the blood samples of patients with MPN, blocking PI3K/AKT could also inhibit the colony forming units of bone marrow progenitor cells, and significantly increased the survival rate of animal model.

CONCLUSIONAKT is a target for the treatment of bone marrow proliferative tumors.