{
  "abstract": "Elevated activity of transcription factor NFE2 is sufficient to cause leukemic transformation in absence of a classical leukemic driver. However, the molecular mechanism promoting NFE2-driven leukemogenesis is not known. Here we report a previously unrecognized role for NFE2 as a key regulator of the oxidative stress response in leukemic cells. Through a comprehensive analysis of NFE2 genomic occupancy and its effect on chromatin accessibility and transcription, we demonstrate that NFE2 regulates glutathione homeostasis as well as the expression of central detoxifying enzymes. NFE2 constituted one of the highest scoring gene dependencies in MLL-AF9-transformed primary leukemic cells under redox stress, substantially more significant than the universally recognized redox regulator NRF2. Consequently, NFE2 knockdown sensitized leukemic cells to GSH depletion, ferroptosis induction, as well as to cytarabine treatment. Deriving an NFE2 RedOx score, we demonstrate that increased NFE2 activity constitutes an independent predictor of inferior outcome in AML patients at diagnosis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hematology/Oncology, Medical Center - University of Freiburg, 79106 Freiburg, Germany",
    "Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany",
    "Faculty of Biology - University of Freiburg, 79106 Freiburg, Germany",
    "Leibniz Institute for Plasma Science and Technology (INP), ZIK Plasmatis, Greifswald, Germany",
    "Rostock University Medical Center, Clinic and Policlinic for Dermatology, Venerology and Allergology, Rostock, Germany"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Anne Marie Staehle",
      "orcid": "0009-0006-7977-0121"
    },
    {
      "affs": [
        1
      ],
      "name": "Florian Perner",
      "orcid": "0000-0003-1010-3321"
    },
    {
      "affs": [
        0
      ],
      "name": "Hans Felix Staehle",
      "orcid": "0000-0001-5082-0646"
    },
    {
      "affs": [
        0
      ],
      "name": "Katharina Gellrich"
    },
    {
      "affs": [
        0
      ],
      "name": "Fiona Preiß",
      "orcid": "0009-0000-6355-0622"
    },
    {
      "affs": [
        0
      ],
      "name": "Annika Grafemeyer",
      "orcid": "0009-0008-5436-712X"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jana Schulze",
      "orcid": "0009-0006-1682-4487"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Luca Funk"
    },
    {
      "affs": [
        0
      ],
      "name": "Albert Gründer"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Julia Berner"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Sander Bekeschus"
    },
    {
      "affs": [
        0
      ],
      "name": "Christoph Koellerer",
      "orcid": "0009-0006-9919-7852"
    },
    {
      "affs": [
        0
      ],
      "name": "Heike L. Pahl",
      "orcid": "0000-0003-2857-2396"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6t33ymfwpn79n.bib",
  "cited_by": 0,
  "doi": "10.1038/s41375-026-03095-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713581/",
  "id": "6t33ymfwpn79n",
  "issns": [
    "0887-6924",
    "1476-5551"
  ],
  "landing_url": "https://doi.org/10.1038/s41375-026-03095-x",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7203735775",
  "pdf_url": "https://www.nature.com/articles/s41375-026-03095-x.pdf",
  "pmcid": "PMC13713581",
  "pmid": "42618699",
  "published": "2026-08-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6t33ymfwpn79n.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:24:06Z",
      "native_id": "PMC13713581",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41375-026-03095-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Acute Myeloid Leukemia Research",
      "subfield": "general"
    }
  ],
  "title": "A novel role for transcription factor NFE2 in redox regulation and chemotherapy resistance in acute myeloid leukemia",
  "title_text": "A novel role for transcription factor NFE2 in redox regulation and chemotherapy resistance in acute myeloid leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:13Z",
  "url": "https://research.draconitic.com/paper/6t33ymfwpn79n",
  "venue": "Leukemia",
  "versions": []
}