•KAT2A maintains cellular phenotypes by limiting transcriptional variability•KAT2A-containing complexes SAGA and ATAC control distinct phenotypes•KAT2A maintenance of leukemia stem cells is likely exerted through KAT2A a histone acetyltransferase recently identified as vulnerability in at least some forms Acute Myeloid Leukemia (AML). Its loss or inhibition prompts out self-renewal into differe...