Comparing to wt mice, dramatically altered gene expression profile was only observed in NPM1-FLT3-ITD mutants which also had higher leukocyte counts, early depletion of common lymphoid progenitors, and a monocytic bias, presenting more acute course of the disease. NPM1 and Nras-mutants, characterized by granulocytic bias, developed AML with a longer latency and a more mature phenotype. Here, NPM1 is linked to acute myeloid leukemia.