biostudies-literatureUnknown6(2)Zhou MChronic myeloid leukemia in the blastic phase (CML-BP) responds poorly to clinical treatments and is usually fatal. In this study, we found that the histone H3 lysine 4 (H3K4) demethylase RBP2 (also called JARID1A and KDM5A) is underexpressed in CML-BP. The RBP2 histone demethylase stimulates leukemia cell differentiation and inhibits cell proliferation. We identified miR-21 was directly downregulated by RBP2 and found that miR-21 downregulated PDCD4 expression in leukemia cells. By binding to miR-21 promoter and by demethylating of trimethylated H3K4 at the miR-21 locus, RBP2 downregulated miR-21 expression. This in turn activated PDCD4. In conclusion, RBP2 epigenetically downregulated miR-21 in blast transformation of CML.Oncotarget1249-61https://www.ebi.ac.uk/biostudies/studies/S-EPMC4359230biostudies-literatureHistone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia.PMC4359230Zhou MHuang TZeng JSun TFu YWang XChen CJia JfalseHistone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia.Chronic myeloid leukemia in the blastic phase (CML-BP) responds poorly to clinical treatments and is usually fatal. In this study, we found that the histone H3 lysine 4 (H3K4) demethylase RBP2 (also called JARID1A and KDM5A) is underexpressed in CML-BP. The RBP2 histone demethylase stimulates leukemia cell differentiation and inhibits cell proliferation. We identified miR-21 was directly downregulated by RBP2 and found that miR-21 downregulated PDCD4 expression in leukemia cells. By binding to miR-21 promoter and by demethylating of trimethylated H3K4 at the miR-21 locus, RBP2 downregulated miR-21 expression. This in turn activated PDCD4. In conclusion, RBP2 epigenetically downregulated miR-21 in blast transformation of CML.2015-01-01T00:00:00Z2015 Jan2025-04-18T15:46:33.737Z2019-03-27T01:48:10ZS-EPMC43592302557581710.18632/oncotarget.2859