AML1-ETO hijacks a distal enhancer of NAT10 to reprogram glutathione metabolism and sustain leukemia stem cell stemness
Epigenetic dysregulation is a defining feature of t(8;21) AML LSCs, extending beyond DNA and histone modifications to the RNA level. RNA acetylation, particularly, N4-acetylcytidine (ac4C), catalyzed by N-acetyltransferase 10 (NAT10) has recently emerged as a pivotal post-transcriptional regulator that enhances mRNA stability and translational efficiency in a locus-specific manner, thereby modulating key cellular programs. Whether RNA ac4C modification represents a selective vulnerability in t(8;21) AML LSCs, and how AML1-ETO interfaces with the RNA epitranscriptomic machinery to sustain stemness remains largely unexplored. Elucidating these mechanisms promises to uncover previously unrecognized, targetable dependencies within LSCs and may inform strategies to eradicate the cellular root of leukemic propagation.