The role of microRNA-196a and microRNA-196b as ERG regulators in acute myeloid leukemia and acute T-lymphoblastic leukemia.

Overexpression of the ETS transcription factor ERG is an adverse prognostic factor in adult patients with acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). We investigated the regulation of ERG by microRNAs and explored their role in hematopoiesis and leukemia. Transfection of precursor molecules of miR-196a and miR-196b induced ERG downregulation and luciferase assays confirmed binding of miR-196a and miR-196b to the ERG 3'UTR. During in vitro differentiation of CD34(+) cells, miR-196b expression decreased with time, indicating a role for miR-196b in early hematopoiesis. In AML, patients with NPM1-mutations had higher levels of miR-196a and miR-196b compared to NPM1-wildtype. In T-ALL patients, miR-196a and miR-196b expression was associated with an immature immunophenotype, and expression of CD34 and CD33. In conclusion, our results identify miR-196a and miR-196b as ERG regulators and implicate a potential role for these miRNAs in acute leukemia.