GSE127999
AMPK links acetyl-coA homeostasis to BET recruitment in acute myeloid leukemia: RNA-seq
Altered metabolism fuels two hallmark properties of cancer cells, unlimited proliferation and differentiation blockade. AMP-activated protein kinase (AMPK) is a master regulator of bioenergetics crucial for glucose metabolism in acute myeloid leukemia (AML) and its inhibition delays leukemogenesis, but whether the metabolic function of AMPK alters AML epigenome remains unknown. Here, we demonstrate that AMPK maintains the epigenome of MLL-rearranged AML by linking acetyl-CoA homeostasis to BET bromodomain protein recruitment to chromatin. AMPK deletion reduced acetyl-CoA and histone acetylation, displacing BET proteins from chromatin in leukemia-initiating cells (LICs). In both mouse and patient-derived xenograft AML models, treating with AMPK and BET inhibitors synergistically suppressed AML. Our results provide a therapeutic rationale to target AMPK and BET for AML therapy. Overall design: RNA-seq of sorted AMPK WT or KO leukemia-GMP cells, with three replicates of each.