To investigate the molecular mechanisms associated with AML progression in the presence of Dnmt3aR878H and Npm1cA initiating mutations, we utilized a mouse model with a heterozygous germline Dnmt3aR878H/+ mutation (26) and a conditional Npm1cA/+ allele (24, 27), along with a tamoxifen-inducible flippase transgene, used to activate the Npm1 mutation. Here, NPM1 is linked to acute myeloid leukemia.