A critical role of epigenetic inactivation of miR-9 in EVI1^high pediatric AML.

ABSTRACT: Ectopic Viral Integration site 1 (EVI1) upregulation is implicated in 10-25% of pediatric acute myeloid leukemia (AML) and has an inferior outcome with current chemotherapy regimens. Here we report that EVI1 upregulation is associated with methylation of the miR-9 promoter and correlated with downregulation of miR-9 in human AML cell lines and bone marrow (BM) cells from pediatric patients. Reactivation of miR-9 by hypomethylating agents and forced expression of miR-9 in EVI1^high leukemia cell lines and primary leukemia cells results in apoptosis and decreased proliferation of EVI1^high leukemia cells. Furthermore, re-expression of miR-9 delays disease progression in EVI1^high leukemia-xenograft mice. Our results suggest that EVI1-induced hypermethylation and

SUBMITTER: Mittal N 

PROVIDER: S-EPMC6391809 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature