Cooperative mutations with Npm1cA included SB insertion patterns consistent with activation of Csf2 (observed in 48% of tumors) and Flt3. Both granulocyte-macrophage colony stimulating factor (CSF2) and the tyrosine kinase receptor FLT3 are frequently mutated in human AML with FLT3 mutations commonly co-occurring with NPM1 mutations (123–125). Here, NPM1 is linked to acute myeloid leukemia.