Transcriptional rewiring by enhancer methylation in CBFA2T3-GLIS2-driven pediatric acute megakaryoblastic leukemia.

ABSTRACT: Resistance to chemotherapy and subsequent relapse remain the primary challenge in pediatric acute myeloid leukemia (pAML), particularly in CBFA2T3-GLIS2 (C/G) fusion-positive acute megakaryoblastic leukemia. Here we demonstrate that the C/G fusion drives extensive DNA methylation changes and oncogenic enhancer activation at cis-regulatory elements (CREs), reshaping gene expression. This multi-omics analysis reveals a distinct hypermethylation pattern at promoters of up-regulated genes in C/G⁺ pAML across patient samples (n = 24) and representative cell lines, notably enriched in adhesion-related, TGFβ, or Wnt signaling pathways. Hypermethylated regions adjacent to transcription start sites (TSS) maintain open chromatin with H3K27ac enrichment, supporting a mechanism of

SUBMITTER: Choudhury SR 

PROVIDER: S-EPMC12552947 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature