In contrast, our pharmacologic and genetic results indicate that the catalytic activity of KAT6A plays a more limited role in KMT2Ar leukemogenicity, while targeting the whole KAT6A protein dramatically affects leukemic potential in murine KMT2A::MLLT3 AML.<h4>Conclusion</h4>Our study indicates that inhibiting KAT6A KAT activity holds compelling promise for KAT6Ar AML patients. Here, KMT2A is linked to acute myeloid leukemia.