By using a mouse bone marrow model bearing the common AML-initiating mutations in DNA methyltransferase 3 α (DNMT3A) and nucleophosmin 1 (NPM1), the work provides further evidence for the role of the signaling orchestrator GRB2-associated–binding protein 2 (GAB2) in AML progression, positioning GAB2 as a potential therapeutic target. The gene discussed is GAB2; the disease is acute myeloid leukemia.