Mir-130a Is Aberrantly Overexpressed in Adult Acute Myeloid Leukemia with t(8;21) and Its Suppression Induces AML Cell Death

Emerging evidence has revealed that miRNAs can function as oncogenes or tumor suppressor genes in leukemia. By profiling miRNA expression across a cohort (n=156) with de novo acute myeloid leukemia (AML), we identified miR-130a as significantly overexpressed in AML with t(8;21). Expression of miR-130a decreased significantly once patients with t(8;21) achieved complete remission, but increased sharply at the time of relapse. In patients with t(8;21) AML, KIT mutational status was associated with miR-130a expression - with higher expression associated with KIT activating mutations. Increased miR-130a expression in t(8;21) AML was associated with worse event-free survival, however no impact on overall survival was observed. Knockdown of RUNX1/RUNX1T1 (AML1/ETO) protein in the SKNO-1 cell line resulted in decrease of expression of miR-130a. Direct binding of RUNX1/RUNX1T1 fusion protein with the promoter sequence of miR-130a was detected with luciferase reporter gene assay. Following miR-130a knockdown, SKNO-1 demonstrated increased sensitivity to etoposide. Taken together, our data suggest that miR-130a is directly activated by RUNX1/RUNX1T1, and can be used to predict leukemia burden, event-free survival and chemotherapy sensitivity in AML with t(8;21).