Increased anti-leukemic activity of decitabine via AR-42-induced upregulation of miR-29b: a novel epigenetic-targeting approach in acute myeloid leukemia.

摘要: Histone deacetylase (HDAC) inhibitors either alone or in combination with hypomethylating agents have limited clinical effect acute myeloid leukemia (AML). Previously, we demonstrated that AML patients higher miR (microRNA)-29b expression had better response to the agent decitabine. Therefore, an increase miR-29b preceding decitabine treatment may provide a therapeutic advantage. We previously showed is suppressed by repressor complex includes HDACs. Thus, HDAC inhibition expression. hypothesized priming cells novel inhibitor (HDACI) AR-42 would result increased via upregulation of miR-29b. Here, show potent HDACI AML, increasing levels and leading downregulation known targets (that is, SP1, DNMT1, DNMT3A DNMT3B). then sequential administration followed resulted stronger anti-leukemic activity vitro vivo than drug alone. These preclinical results before represent promising, approach paradigm shift regard epigenetic-targeting compounds where has been traditionally given HDACIs.