The Outcome Of HDAC3 Suppression Combinating With Conventional Chemotherapy In Drug Resisitant Acute Myeloid Leukemia

Objective: To study the efficacy of HDAC3 suppression combined with conventional chemotherapy in multidrug resistant leukemia cell lines,primary leukemia cells and MLL-AF9 induced AML mouse model.Method: The growth inhibition rates of multidrug resistant leukemia cell lines THP-1 and K562/Doxo,which were treated with conventional chemotherapy and HDAC3 inhibition genetically or pharmalogically were detected by CCK-8 assay.The apoptosis,which resulted by HDAC3 suppression combined with classic chemotherapy agents in primary leukemia cells from paitnets with AML were measured by flow cytometry.MLL-AF9 induced AML mouse model was established to evaluate the efficacy of targeting HDAC3 combined with conventional chemotherapy.Result: 1.Inhibiting HDAC3 sensitizes leukemia cells to chemotherapy drugs-induced death in multidrug resistant cell lines.2.Synergistic antileukemic effect of HDAC3 suppression and conventional chemotherapy in the AML patients’ primary cells.3.Combining HDAC3 suppression with classic drug therapy prolongs the survival of AML mice and reduces the leukemia burden.Conclusion:Inhibiting HDAC3 can improve the efficacy of chemotherapy in AML.