Using retroviral constructs, we found that overexpression of Gab2 (but not Pak1) induced significant (P < 1 × 10–10 by 2-sided, 1-sample t test at 10 weeks) expansion in hematopoietic cells with Npm1cA and Dnmt3aR878H mutations and accelerated the development of AML; these effects were dependent on the preexisting mutations in Dnmt3a and Npm1. Here, NPM1 is linked to acute myeloid leukemia.