{
  "id": 13002582,
  "title": "CBFA2T3-GLIS2 establishes transcriptionally permissive enhancer hypermethylation associated with venetoclax response in pediatric AML",
  "url": "https://urgent.news/2026/10/08/cbfa2t3-glis2-establishes-transcriptionally-permissive-enhancer",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-10-08T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756000v1?rss=1"
  },
  "original_language": "en",
  "account": "A recent study has uncovered a new mechanism in pediatric acute myeloid leukemia (AML) that links hypermethylation of specific enhancer regions to increased sensitivity to the drug venetoclax. Researchers identified this as a unique feature of a high-risk subtype known as CBFA2T3-GLIS2.\n\nUsing samples from primary AML patients and a cellular model, the team found that hypermethylated regions near active transcription elements are enriched for ERG/ETS-like motifs. Interestingly, when the gene DNMT3B, crucial for DNA methylation, was lost, the methylation-associated gene expression changed, and venetoclax sensitivity increased both in vitro and in vivo.\n\nFollowing venetoclax treatment, AML cells with DNMT3B loss exhibited reduced disease burden and prolonged survival. Moreover, combining azacitidine or decitabine with venetoclax led to apoptosis-related transcriptional programs and mitochondrial depolarization, suggesting a synergistic effect.\n\nThese findings demonstrate that hypermethylated active cis-regulatory elements are associated with the aggressive leukemic transcriptional state and venetoclax response in CBFA2T3-GLIS2-positive pediatric AML.",
  "summary": "CBFA2T3-GLIS2 (C/G) defines a high-risk pediatric AML subtype in which de novo enhancer rewiring sustains an aggressive leukemic transcriptional state. The early epigenomic mechanisms reinforcing this program and linking it to leukemic survival remain incompletely defined. Here, we identify enhancer-proximal hypermethylation as a noncanonical, transcription-permissive feature of C/G AML. Using…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}