HDAC2-miR183-5p epigenetic circuit contributes to the growth of Philadelphia chromosome-positive B cell acute lymphoblastic leukemia via PTEN/AKT and c-MYC signaling pathway.

Philadelphia chromosome-positive B cell acute lymphoblastic leukemia [Ph(+) B-ALL] is a hematological malignancy with a poor prognosis. Epigenetic abnormalities, especially abnormal histone acetylation and microRNA (miRNA) dysregulation, are a group of epigenetic patterns that contribute to leukemia progression. However, their regulatory mechanisms in Ph(+) B-ALL have not been fully elucidated. In this study, we identified that miR-183-5p is significantly downregulated in Ph(+) B-ALL and associated with poor prognosis. Moreover, we found that the BCR-ABL fusion gene is a key target gene of miR-183-5p. MiR-183-5p directly targets the BCR-ABL gene and induces cell apoptosis via PTEN/AKT and c-MYC signaling pathways. In addition, a histone deacetylase inhibitor could mitigate the suppressive effects of HDAC2 on miR-183-5p by promoting promoter acetylation, thereby enhancing cell apoptosis. In conclusion, our results indicate that miR-183-5p is a potential biomarker and suggest that a novel HDAC2-miR-183-5p epigenetic circuitry regulation may be involved in the pathogenesis of Ph(+) B-ALL. Taken together, These findings provide new insights into the design of promising molecular-targeted drugs for Ph(+) B-ALL.