KAT6A chimeras form a self-reinforcing epigenetic module with NURF and MLL/COMPASS to sustain AML.

ABSTRACT:

Background

KAT6A-CBP (K/C) and KAT6A-P300 (K/P) fusions are recurrent genetic alterations in acute myeloid leukemia (AML) associated with poor prognosis. Despite their strong oncogenic potential, the mechanisms underlying their genomic targeting and leukemogenic function remain unclear. A major challenge has been their large size, which has impeded preclinical model development and mechanistic studies.

Results

We employ a domain-focused truncation strategy to generate de novo murine models of K/C and K/P fusions, which faithfully recapitulate the morphological, immunophenotypic, and transcriptomic features of KAT6A-rearranged AML. Genomic profiling reveals that KAT6A fusions preferentially localize to H3K4me2/3-marked regions, while biochemical analyses uncover that KAT6A in

SUBMITTER: Lv J 

PROVIDER: S-EPMC12366150 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature