{
  "abstract": "Acute myeloid leukemia (AML) is driven by genetic alterations and non-mutational mechanisms that disrupt normal hematopoiesis and support leukemic cell survival. While the mutational landscape of AML is well characterized, the non-genetic processes sustaining leukemic maintenance remain less understood. Using human AML cells and murine models, we identify BCL2-associated transcription factor 1 (BCLAF1) as a key regulator of leukemic progression through control of mRNA processing. BCLAF1 physically associates with core spliceosome components and regulates alternative splicing programs in leukemic cells. Mechanistically, BCLAF1 is required for productive splicing of activating transcription factor 4 (ATF4) mRNA, thereby sustaining ATF4 protein levels and downstream metabolic gene expression programs. Loss of BCLAF1 reduces ATF4 levels, leading to impaired de novo amino acid biosynthesis and increased sensitivity to venetoclax. Together, these findings uncover a previously unrecognized mechanism linking RNA splicing control to metabolic adaptation in AML, identifying BCLAF1 as a potential therapeutic vulnerability.",
  "abstract_shown": true,
  "affiliations": [
    "Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, CSIC-Universidad de Sevilla-Universidad Pablo de Olavide, 41092 Seville, Spain.",
    "Departamento de Genética, Universidad de Sevilla, 41012 Seville, Spain.",
    "Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.",
    "Department of Molecular Biotechnology and Health sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.",
    "Center for Human Technologies, Istituto Italiano di Tecnologia (IIT), Genova, Italy.",
    "Departamento de Biología Celular, Universidad de Sevilla, 41012 Seville, Spain.",
    "Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO.",
    "Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA."
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Laura López-Hernández",
      "orcid": "0000-0003-3649-3110"
    },
    {
      "affs": [
        2
      ],
      "name": "Stephanie J. Crowley",
      "orcid": "0000-0002-6665-0108"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sara Cea-Sánchez",
      "orcid": "0000-0001-5476-2156"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ricardo de Arellano",
      "orcid": "0009-0001-9289-726X"
    },
    {
      "affs": [
        2
      ],
      "name": "Neetij Krishnan",
      "orcid": "0000-0001-5746-2810"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Patrick Toolan-Kerr",
      "orcid": "0000-0002-7970-649X"
    },
    {
      "affs": [
        2
      ],
      "name": "Lynn White"
    },
    {
      "affs": [
        3
      ],
      "name": "Domenico Ignoti"
    },
    {
      "affs": [
        0
      ],
      "name": "Emily Soto-Hidalgo",
      "orcid": "0009-0000-1824-2436"
    },
    {
      "affs": [
        4
      ],
      "name": "Stefano Gustincich",
      "orcid": "0000-0002-2749-2514"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Román González-Prieto",
      "orcid": "0000-0001-8997-2321"
    },
    {
      "affs": [
        4
      ],
      "name": "Luca Pandolfini",
      "orcid": "0000-0003-1444-8167"
    },
    {
      "affs": [
        3
      ],
      "name": "Isaia Barbieri"
    },
    {
      "affs": [
        0
      ],
      "name": "Patricia Altea-Manzano",
      "orcid": "0000-0002-7075-2051"
    },
    {
      "affs": [
        2
      ],
      "name": "Jeffrey A. Magee",
      "orcid": "0000-0002-0766-4200"
    },
    {
      "affs": [
        6
      ],
      "name": "Francesca Ferraro",
      "orcid": "0000-0003-0098-9819"
    },
    {
      "affs": [
        2
      ],
      "name": "Samuel J. Taylor",
      "orcid": "0000-0002-9468-8752"
    },
    {
      "affs": [
        2,
        7
      ],
      "name": "Jeffrey J. Bednarski",
      "orcid": "0000-0001-6902-0876"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gonzalo Millán-Zambrano",
      "orcid": "0000-0002-4530-6359"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dhrpfk38fjjm5.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aeg0571",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13743010/",
  "id": "dhrpfk38fjjm5",
  "issns": [
    "2375-2548"
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  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
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  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biomedicine and Life Sciences"
    ],
    [
      "heading",
      "Cancer"
    ],
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      "heading",
      "Life Sciences"
    ],
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      "heading",
      "Research Article"
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      "heading",
      "SciAdv r-articles"
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  "openalex": null,
  "pdf_url": null,
  "pmcid": "PMC13743010",
  "pmid": "42981398",
  "published": "2026-11-04",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/dhrpfk38fjjm5.ris",
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  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Life Sciences",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "heading:Cancer",
      "subfield": "oncology"
    }
  ],
  "title": "BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia",
  "title_text": "BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:23:44Z",
  "url": "https://research.draconitic.com/paper/dhrpfk38fjjm5",
  "venue": "Science Advances",
  "versions": []
}