{
  "abstract": "DNA methylation dynamics shape hematopoietic differentiation and leukemogenesis, yet how the dioxygenase TET2-frequently mutated in myeloid malignancies-directs lineage-specific regulatory programs remains unclear. Here, we integrated DNA methylation, chromatin accessibility, three-dimensional (3D) genome architecture, transcriptional profiling, and TET2 chromatin occupancy to define TET2-dependent control of human myeloid commitment. We found that TET2-bound regulatory regions gain short- and long-range chromatin interactions and that a distinct subset of distal, enhancer-enriched sites undergoes TET2-driven demethylation and activation. Among these, we identified and functionally validated an AGO2 myeloid-specific intragenic enhancer that is frequently hypermethylated in patients with TET2-mutant acute myeloid leukemia. AGO2 expression stratifies patient survival, and AGO2 depletion abrogates leukemic engraftment in vivo. These findings uncover a TET2-AGO2 regulatory axis that integrates epigenetic remodeling, 3D genome reorganization, and leukemic fitness, and they highlight AGO2 as a potential biomarker and therapeutic target in myeloid leukemia.",
  "abstract_shown": true,
  "affiliations": [
    "Epigenetic Control of Haematopoiesis Group, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Spain.",
    "Stem Cell Biology, Developmental Leukemia and Immunotherapy Group, Josep Carreras Leukaemia Research Institute (IJC), Campus Hospital Clínic, Barcelona, Spain.",
    "Red de Terapias Avanzadas (TERAV), Instituto de Salud Carlos III, Madrid, Spain.",
    "Endocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu Fabra, 08003 Barcelona, Spain.",
    "Department of Hematology, Hospital Clinic Barcelona, Barcelona, Spain.",
    "Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.",
    "Nuclear Architecture in Leukemia Group, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, Badalona, Spain.",
    "Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Munich, German Research Center for Environmental Health (HMGU), Munich, Germany.",
    "German Cancer Consortium (DKTK), partner site Munich, a partnership between DKFZ and University Hospital LMU Munich, Munich, Germany.",
    "Pediatric Cancer Centre Barcelona-Institut de Recerca Sant Joan de Deu (PCCB-SJD), Barcelona, Spain.",
    "Department of Biomedicine, University of Barcelona, Barcelona, Spain.",
    "Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.",
    "Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Aleksey Lazarenkov",
      "orcid": "0000-0003-0652-8116"
    },
    {
      "affs": [
        0
      ],
      "name": "Gemma Valcárcel",
      "orcid": "0000-0003-0494-9128"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Alba Martinez",
      "orcid": "0000-0001-7514-260X"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Clara Berenguer",
      "orcid": "0000-0003-4190-8085"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna V. López-Rubio",
      "orcid": "0000-0001-8664-6205"
    },
    {
      "affs": [
        0
      ],
      "name": "Mireia Obiols",
      "orcid": "0000-0003-3323-5239"
    },
    {
      "affs": [
        0
      ],
      "name": "Claudia Fontanet"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana Barba"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Juan José Rodríguez-Sevilla",
      "orcid": "0000-0002-4741-7925"
    },
    {
      "affs": [
        6
      ],
      "name": "Gregoire Stik",
      "orcid": "0000-0002-1404-1992"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Irmela Jeremias",
      "orcid": "0000-0003-1773-7677"
    },
    {
      "affs": [
        1,
        2,
        9,
        10,
        11,
        12
      ],
      "name": "Pablo Menendez",
      "orcid": "0000-0001-9372-1007"
    },
    {
      "affs": [
        0
      ],
      "name": "José Luis Sardina",
      "orcid": "0000-0002-8493-3937"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5j8fp53wm9ybk.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aee5701",
  "fulltext_url": "https://europepmc.org/articles/PMC13693683",
  "id": "5j8fp53wm9ybk",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aee5701",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7223282769",
  "pdf_url": "https://europepmc.org/articles/PMC13693683?pdf=render",
  "pmcid": "PMC13693683",
  "pmid": "42912985",
  "published": "2026-10-23",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/5j8fp53wm9ybk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aee5701",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aee5701"
    },
    {
      "first_seen": "2026-10-30T12:20:03Z",
      "native_id": "MED:42912985",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42912985"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Acute Myeloid Leukemia Research",
      "subfield": "general"
    }
  ],
  "title": "TET2-driven activation of AGO2 links epigenetic remodeling to myeloid commitment and leukemia",
  "title_text": "TET2-driven activation of AGO2 links epigenetic remodeling to myeloid commitment and leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:03Z",
  "url": "https://research.draconitic.com/paper/5j8fp53wm9ybk",
  "venue": "Science Advances",
  "versions": []
}