{
  "abstract": "CDK6 and STAT5B are well-established oncogenic drivers, but their interplay during transformation remains poorly understood. Here, we demonstrate that simultaneous genetic deletion of Cdk6 and Stat5b in an NPM-ALKTg/+ mouse model completely prevents tumor formation. Immature DN2/3 thymocytes are identified as the cellular origin of ALK-driven malignancy. Single-cell transcriptomics reveals a tumor-specific differentiation trajectory that is fully disrupted by combined Cdk6/Stat5b loss, coinciding with a developmental shift. We uncover shared transcriptional targets of CDK6 and STAT5B involved in cell-cycle regulation and apoptosis at the tumor initiation stage. In human ALCL cells, dual deletion of CDK6 and STAT5B induces context-dependent synthetic lethality, exposing a potential therapeutic vulnerability. A transcriptional signature derived from CDK6/STAT5B-dependent tumor initiation genes identifies a high-risk subgroup of ALCL patients with worse survival. Together, these findings establish a molecular link between thymocyte development, the crosstalk of CDK6 and STAT5B, oncogenic signaling, and clinical outcome in ALCL.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biological Sciences and Pathobiology, Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria.",
    "Department of Internal Medicine I (Oncology, Hematology, Clinical Immunology, and Rheumatology), Saarland University Medical School, Homburg, Germany.",
    "Department of Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.",
    "Department of Experimental Medicine, University of Genoa, Genoa, Italy.",
    "Department of Biological Sciences and Pathobiology, Unit of Pathology, University of Veterinary Medicine, Vienna, Austria.",
    "Department of Pathology, Medical University of Vienna, Vienna, Austria.",
    "Christian Doppler Laboratory for Applied Metabolomics, Medical University of Vienna, Vienna, Austria.",
    "Center for Biomarker Research in Medicine, CBmed GmbH, Graz, Austria.",
    "Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.",
    "Department of Molecular Biology, Umeå University, Umeå, Sweden.",
    "Department of Biosciences and Medical Biology, Paris Lodron University of Salzburg, Salzburg, Austria.",
    "University of Innsbruck, Innsbruck, Austria.",
    "Department of Biological Sciences and Pathobiology, Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria. Karoline.Kollmann@vetmeduni.ac.at.",
    "Department of Biological Sciences and Pathobiology, Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria. Thorsten.Klampfl@vetmeduni.ac.at."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jonatan Kendler",
      "orcid": "0000-0002-2470-4868"
    },
    {
      "affs": [
        0
      ],
      "name": "Maximilian Sexl"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessia Schirripa",
      "orcid": "0000-0001-5446-9136"
    },
    {
      "affs": [
        0
      ],
      "name": "Elisabeth Gamper",
      "orcid": "0009-0007-8439-4148"
    },
    {
      "affs": [
        0
      ],
      "name": "Hager El Kersh",
      "orcid": "0009-0006-5312-6039"
    },
    {
      "affs": [
        0
      ],
      "name": "Barbara Maurer"
    },
    {
      "affs": [
        0
      ],
      "name": "Reinhard Grausenburger"
    },
    {
      "affs": [
        0
      ],
      "name": "Klavdija Krause",
      "orcid": "0000-0002-8383-1330"
    },
    {
      "affs": [
        1
      ],
      "name": "Dua Shahid",
      "orcid": "0009-0001-6028-4696"
    },
    {
      "affs": [
        2
      ],
      "name": "Alexander Pichler"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Giorgia Damonte",
      "orcid": "0009-0000-5739-3966"
    },
    {
      "affs": [
        0
      ],
      "name": "Tania Brandstoetter",
      "orcid": "0000-0003-4037-5352"
    },
    {
      "affs": [
        0
      ],
      "name": "Michaela Prchal-Murphy"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Stefania Massari"
    },
    {
      "affs": [
        4
      ],
      "name": "Sabine Lagger",
      "orcid": "0000-0002-3032-9910"
    },
    {
      "affs": [
        4,
        5,
        6,
        7,
        8,
        9
      ],
      "name": "Lukas Kenner",
      "orcid": "0000-0003-2184-1338"
    },
    {
      "affs": [
        10
      ],
      "name": "Richard Moriggl",
      "orcid": "0000-0003-0918-9463"
    },
    {
      "affs": [
        1,
        2,
        8
      ],
      "name": "Philipp B Staber"
    },
    {
      "affs": [
        0,
        11
      ],
      "name": "Veronika Sexl"
    },
    {
      "affs": [
        0
      ],
      "name": "Sebastian Kollmann"
    },
    {
      "affs": [
        12
      ],
      "name": "Karoline Kollmann",
      "orcid": "0000-0002-7937-4245"
    },
    {
      "affs": [
        13
      ],
      "name": "Thorsten Klampfl",
      "orcid": "0000-0002-6666-9773"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5a4tcn5sve02b.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77466-4",
  "fulltext_url": "https://europepmc.org/articles/PMC13672290",
  "id": "5a4tcn5sve02b",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42881166",
  "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",
      "2734|Lymphoma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7213232609",
  "pdf_url": "https://europepmc.org/articles/PMC13672290?pdf=render",
  "pmcid": "PMC13672290",
  "pmid": "42881166",
  "published": "2026-09-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5a4tcn5sve02b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42881166",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42881166"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Lymphoma Diagnosis and Treatment",
      "subfield": "general"
    }
  ],
  "title": "Ablation of CDK6 and STAT5B rewires T cell developmental dynamics and prevents ALK⁺ lymphoma formation.",
  "title_text": "Ablation of CDK6 and STAT5B rewires T cell developmental dynamics and prevents ALK⁺ lymphoma formation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/5a4tcn5sve02b",
  "venue": "Nature communications",
  "versions": []
}