We establish herein a novel protective role for miR-196b in HSPCs that delays AML development driven by coincident Dnmt3a and Flt3ITD mutations whereby Dnmt3a/Flt3-mutant mice with deletion of miR-196b succumb to AML faster than Dnmt3a/Flt3-mutant mice with endogenous miR-196b. The gene discussed is FLT3; the disease is acute myeloid leukemia.