Severity of Npm1^cA/+-mutated AML is dictated by concomitant mutations. The presence of different partner mutations in the Npm1^cA/+-mutated mouse model (Npm1c⁺) variably affects the severity and penetrance of the disease phenotype. In particular, Npm1^cA/+;Nras^G12D/+ mice develop a less aggressive and more differentiated AML than Npm1^cA/+;Flt3^ITD mice. Compound mutant mice carrying Npm1^cA/+;Dnmt3a^R878H mutations do not develop leukemia.⁹  Compound mice co-mutated for Npm1^cA/+ and Idh1/2 genes are expected to be generated for future comparative studies. HSCs, hematopoietic stem cells; WBCs, white blood cells.