Pathogenesis of FLT3-mutated AML and KMT2A-r AML. (A) FLT3-ITD and FLT3-TKD mutations lead to increased downstream signaling from the FLT3 receptor, which thereby promotes increased cell growth, proliferation, and survival. FLT3 inhibitors block this downstream signaling. (B) Binding of the KMT2A protein to menin allows the KMT2A/fusion partner protein to facilitate downstream transcription of HOX and other developmental proteins that contribute to leukemic pathogenesis. Inhibitors of the menin- KMT2A interaction inhibit this transcription. AKT, Akt serine/threonine protein kinases; MAPK, mitogen-activated protein kinases; PI3K, phosphoinositide-3 kinases; STAT5, signal transducer and activator of transcription 5. Created with BioRender.com.