The combined effects of two commonly occurring somatic mutations in AML Nucleophosmin 1 (NPM1) exon 12 mutations (NPM1c) and internal tandem duplications of FLT3 (FLT3-ITD) were examined by crossing conditional Npm1flox − cA/+ with constitutive Flt3ITD/+ to generate Npm1flox − cA/+; Flt3ITD/+ double heterozygous mice, which were then crossed into Mx1-Cre transgenic mice to induce recombination of Npm1flox − cA in HSCs. The gene discussed is FLT3; the disease is acute myeloid leukemia.