---
title: "AML1-ETO targets a distal NAT10 enhancer to alter glutathione metabolism in t(8;21) AML"
id: "pubmed-42679037"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42679037"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42679037/"
doi: "10.1073/pnas.2608310123"
published_at: "2026-09-01T22:13:34.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# AML1-ETO targets a distal NAT10 enhancer to alter glutathione metabolism in t(8;21) AML
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42679037
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42679037/)
- **DOI:** [10.1073/pnas.2608310123](https://doi.org/10.1073%2Fpnas.2608310123)
- **Published At:** 2026-09-01T22:13:34.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Chromosomal translocations can generate oncogenic fusion proteins such as **AML1-ETO**, which are known to reprogram transcription in leukemia stem cells (LSCs) and drive t(8;21) acute myeloid leukemia (AML). - Prior work established that AML1-ETO predominantly occupies gene promoters to induce transcriptional changes in LSCs; it was unclear whether the fusion protein also engages distal regulatory elements. - The authors applied genome-wide profiling (CUT&Tag) for **AML1-ETO** and H3K27ac in primary t(8;21) AML CD34+ cells and in t(8;21) AML cell lines to map binding and active enhancer landscapes. - These profiles revealed AML1-ETO binding at a distal enhancer linked to the RNA N4-acetyltransferase gene **NAT10** (reported as “RNA N4-acetylc…” in the source), indicating recruitment of AML1-ETO beyond promoters. - The title and abstract indicate that this hijacking of a NAT10 distal enhancer reprograms **glutathione metabolism** and sustains **leukemia stem cell stemness**, implying a functional connection between enhancer hijacking, NAT10 regulation, redox/metabolic pathways, and LSC maintenance. - The source text is truncated: details about the specific enhancer coordinates, mechanistic experiments, gene expression changes, metabolic assays, effects on LSC phenotypes, and any therapeutic implications or interventions are not reported in the provided excerpt. - Publication and provenance: Proc Natl Acad Sci U S A; PMID 42679037; DOI 10.1073/pnas.2608310123; publication date listed as 2026 Sep 8 with Epub 2026 Sep 1. Authors are affiliated with Shenzhen University and associated laboratories in China. - Because the abstract in the source is incomplete, specifics of methods, quantitative results, statistical significance, and downstream validation are not available from the provided content and therefore are not asserted here.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 1. # AML1-ETO hijacks a distal enhancer of NAT10 to reprogram glutathione metabolism and sustain leukemia stem cell stemness [Shuyi Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+S&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Shujiao He](https://pubmed.ncbi.nlm.nih.gov/?term=He+S&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Yongwei Su](https://pubmed.ncbi.nlm.nih.gov/?term=Su+Y&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-2 "Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Lei Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+L&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Yiran Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Yuanyuan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+Y&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Li Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+L&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Jingfeng Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+J&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#full-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.") Affiliations Expand ### Affiliations * 1 Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China. * 2 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China. * PMID: **42679037** * DOI: [ 10.1073/pnas.2608310123 ](https://doi.org/10.1073/pnas.2608310123) Item in Clipboard # AML1-ETO hijacks a distal enhancer of NAT10 to reprogram glutathione metabolism and sustain leukemia stem cell stemness Shuyi Li et al. Proc Natl Acad Sci U S A. 2026. Show details Display options Display options Format Abstract PubMed PMID Proc Natl Acad Sci U S A Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Proc+Natl+Acad+Sci+U+S+A%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Proc+Natl+Acad+Sci+U+S+A%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42679037/) . 2026 Sep 8;123(36):e2608310123. doi: 10.1073/pnas.2608310123. Epub 2026 Sep 1. ### Authors [Shuyi Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+S&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Shujiao He](https://pubmed.ncbi.nlm.nih.gov/?term=He+S&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Yongwei Su](https://pubmed.ncbi.nlm.nih.gov/?term=Su+Y&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-2 "Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Lei Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+L&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Yiran Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+Y&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Yuanyuan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+Y&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Li Yu](https://pubmed.ncbi.nlm.nih.gov/?term=Yu+L&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China."), [Jingfeng Zhou](https://pubmed.ncbi.nlm.nih.gov/?term=Zhou+J&cauthor_id=42679037)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42679037/#short-view-affiliation-1 "Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China.") ### Affiliations * 1 Shenzhen University International Cancer Center, Department of Hematology and Oncology, Hematology Institution, Shenzhen University General Hospital, International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China. * 2 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China. * PMID: **42679037** * DOI: [ 10.1073/pnas.2608310123 ](https://doi.org/10.1073/pnas.2608310123) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract Chromosomal translocations produce oncogenic fusion proteins such as AML1-ETO, which predominantly occupy gene promoters to induce transcriptional reprogramming in leukemia stem cells (LSCs), consequently driving the pathogenesis of t(8;21) acute myeloid leukemia (AML). However, whether AML1-ETO is recruited to additional regulatory DNA elements to orchestrate oncogenic gene expression programs has not been fully addressed. Here, we define AML1-ETO and H3K27ac CUT&Tag landscapes in primary t(8;21) AML CD34+ cells and t(8;21) AML cell lines, revealing AML1-ETO binding at a distal enhancer of the RNA N4-acetylc
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