In the current study, we have analyzed and compared the genetic, phenotypic, and transcriptomic features of AML driven by a combination of FLT3ITD TET2, FLT3ITDDNMT3A, or FLT3ITD TET2 DNMT3A, utilizing AML models, patient cells, and transcriptomic data derived from both mice and humans. Here, DNMT3A is linked to acute myeloid leukemia.