RESUMO
<p><b>OBJECTIVE</b>To study the therapeutic effect of AKT inhibitor on the myeloproliferative neoplasms(MPN) and its significanse.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>AKT is a target for the treatment of bone marrow proliferative tumors.</p>
RESUMO
<p><b>OBJECTIVE</b>To study the function of ZNF300 in the megakaryocytes differentiation and proliferation.</p><p><b>METHODS</b>Public data analysis of ZNF300 expression and megakaryocyte culture were used to reveal the correlation of ZNF300 expression with leukemia and megakaryocyte differetniation; ZNF300 overexpression was mediated by lentiviral or retroviral infection, and the differentiation and proliferation of K562 cells and primary mouse bone marrow cells to magekaryocytes were measured by flow cytometry, MTT assay and colony-forming test; the ZNF300 subcellular localization was tested by separating cytosolic and nuclear extracts combined with Western blotting. The dual-luciferase assay and ChIP-qPCR were used to study ZNF300 target gene.</p><p><b>RESULTS</b>ZNF300 expression upregulation correlated with megakaryoyte differentiation; over-expression of ZNF300 promoted CD41 and CD61 expression, inhibited cell cycle progress, and could reduce colony-forming unit. The ZNF300 locolized in nuclear and regulated C-MYC expression.</p><p><b>CONCLUSION</b>ZNF300 promotes megakaryocyte differentiation.</p>