{
  "abstract": "Clonal hematopoiesis of indeterminate potential (CHIP) has been well-characterized in patients receiving chemotherapy and hematopoietic cell transplantation. However, its immunologic relevance and potential role in modulating chimeric antigen receptor T-cell (CAR-T) therapy-related toxicities, inflammation, and clinical outcomes remains incompletely defined. In this exploratory study of 104 CAR-T recipients, we investigated the prognostic impact of pre-existing CHIP clones on toxicity and survival, and examined CHIP-associated inflammatory proteomic signatures leveraging longitudinal serum samples. Overall CHIP status was not associated with inflammatory toxicities, outcomes, or systemic inflammatory profiles. Analysis of clonal dynamics revealed TP53- and ASXL1-mutated clones to be the dominant expanding CHIP clones post-infusion, whereas DNMT3A- and PPM1D-mutated clones showed reduced clonal abundance over time. Notably, TP53-mutated CHIP was linked to lower platelet and hemoglobin levels, a higher baseline CAR-HEMATOTOX score, inferior clinical outcomes, and a distinct inflammatory signature. These findings identify TP53-mutated CHIP in CAR-T-treated patients as a high-risk CHIP genotype compared with other CHIP mutations. Importantly, patients who developed treatment-emergent myeloid neoplasms after CAR T-cell therapy exhibited distinct patterns of clonal expansion and inflammatory profiles. Together, these findings support a risk-adapted approach prioritizing longitudinal monitoring of TP53-mutated CHIP, especially in patients with high CAR-HEMATOTOX scores who develop cytopenias.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine III, University Hospital, LMU Munich, Munich, Germany",
    "Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany",
    "The Bavarian Cancer Research Center (BZKF), Munich, Germany",
    "Experimental Leukemia and Lymphoma Research (ELLF), LMU Munich, Munich, Germany",
    "Laboratory for Leukemia Diagnostics (LFL), LMU Munich, Munich, Germany",
    "German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany",
    "Laboratory for Precision Immunotherapy, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany",
    "Metabolomics and Proteomics Core Facility, Helmholtz Zentrum Munich—German Research Center for Environmental Health, Munich, Germany",
    "Department of Medicine III, Klinikum Rechts der Isar, Technical University of Munich (TUM) Hospital, Munich, Germany",
    "Department of Internal Medicine 5-Hematology and Oncology, University Hospital, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Giulia Rappa",
      "orcid": "0009-0001-1050-0258"
    },
    {
      "affs": [
        0,
        2,
        3,
        4,
        5
      ],
      "name": "Frank Ziemann"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kieron White"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Linus Kruk"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Samar Shamas",
      "orcid": "0009-0001-3837-8055"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Amelie Muth",
      "orcid": "0009-0009-6900-7212"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Kayleen Shi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Cristina Zucchinetti",
      "orcid": "0000-0002-8529-6490"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Savanna Süß",
      "orcid": "0009-0009-2900-5351"
    },
    {
      "affs": [
        4
      ],
      "name": "Maja Rothenberg-Thurley"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessandra Holzem"
    },
    {
      "affs": [
        0,
        6
      ],
      "name": "Tobias Tix"
    },
    {
      "affs": [
        7
      ],
      "name": "Agnese Petrera"
    },
    {
      "affs": [
        4
      ],
      "name": "Bianka Ksienzyk"
    },
    {
      "affs": [
        4
      ],
      "name": "Charlotte Bentenrieder"
    },
    {
      "affs": [
        2,
        5,
        8
      ],
      "name": "Katharina S. Götze",
      "orcid": "0000-0002-6276-8002"
    },
    {
      "affs": [
        9
      ],
      "name": "Fabian Müller",
      "orcid": "0000-0001-5487-5839"
    },
    {
      "affs": [
        0,
        1,
        2,
        4,
        5
      ],
      "name": "Veit Bücklein",
      "orcid": "0000-0001-7391-7280"
    },
    {
      "affs": [
        0,
        2,
        5,
        6
      ],
      "name": "Kai Rejeski",
      "orcid": "0000-0003-3905-0251"
    },
    {
      "affs": [
        0,
        1,
        2,
        4,
        5
      ],
      "name": "Marion Subklewe",
      "orcid": "0000-0001-9154-9469"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3fdv8devd0gwr.bib",
  "cited_by": 1,
  "doi": "10.1038/s41375-026-03083-1",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13713554/",
  "id": "3fdv8devd0gwr",
  "issns": [
    "0887-6924",
    "1476-5551"
  ],
  "landing_url": "https://doi.org/10.1038/s41375-026-03083-1",
  "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"
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  "openalex": "W7204097425",
  "pdf_url": "https://www.nature.com/articles/s41375-026-03083-1.pdf",
  "pmcid": "PMC13713554",
  "pmid": "42637877",
  "published": "2026-08-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3fdv8devd0gwr.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:24:05Z",
      "native_id": "PMC13713554",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41375-026-03083-1"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Acute Myeloid Leukemia Research",
      "subfield": "general"
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  ],
  "title": "TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy",
  "title_text": "TP53-mutant CHIP defines a pro-inflammatory phenotype and predicts adverse outcomes after CAR T-cell therapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:12Z",
  "url": "https://research.draconitic.com/paper/3fdv8devd0gwr",
  "venue": "Leukemia",
  "versions": []
}