Although coincident Flt3/ITD and Wt1/R394W mutations do not appear sufficient to consistently recapitulate human AML in a mouse model, our results demonstrate that Flt3/ITD and Wt1/R394W mutations are capable of cooperation, resulting in a more aggressive disease than resulted from either individual mutant genotype alone. This evidence concerns the gene FLT3 and acute myeloid leukemia.