{
  "abstract": "Chronic myelomonocytic leukemia (CMML) is a heterogeneous myeloid neoplasm with highly variable prognosis. TET2 is mutated in ∼60% of patients, previously linked to favorable outcomes. However, no study has quantitatively characterized TET2 variant allele frequency (VAF) as a continuous, nonlinear prognostic variable, nor leveraged it to refine contemporary CMML risk stratification systems. We examined the prognostic role of TET2 VAF in 1206 patients across a UK discovery cohort (DC; TET2-mutated, 433/645 [67%]), an international validation cohort (validation cohort 1 [VC1]; TET2-mutated, 141/291 [48%]), and a French CD14⁺ monocyte-sequenced cohort (VC2; TET2-mutated, 176/270 [65%]). Segmented regression of TET2 VAF distributions reproducibly identified two inflection points (DC, 32%/55%; VC1, 33%/54%; VC2, 36%/56%), implying consistent subdivision of TET2 mutation burden across CMML of epidemiological (and potentially biological) relevance. Restricted cubic spline Cox regression revealed a nonlinear relationship between TET2 VAF and survival, with risk lowest near VAF 39% (the empirical first quartile), whereas patients with TET2 wild-type status had hazards comparable to patients with high VAF. Capitalizing on this continuous relationship, we constructed TET2-VAF-adjusted CMML-specific Prognostic Scoring System-Molecular, Groupe Francais des Myelodysplasies model, and Mayo Molecular Model scores by adding a per-integer VAF adjustment to each patient's original score. Across cohorts and prognostic tools, the adjusted scores improved discrimination (Harrell C-index gain in 16/18 comparisons; integrated discrimination improvement significant in all 18 comparisons; P < .01) and group-level stratification for overall survival and acute myeloid leukemia-free survival. These findings suggest that TET2 VAF represents a continuous prognostic variable in CMML and provide a robust, reproducible framework for refining standard risk stratification systems.",
  "abstract_shown": true,
  "affiliations": [
    "Epigenetics of Haematopoiesis Laboratory, Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom.",
    "Division of Hematology, National Taiwan University Hospital, Taipei, Taiwan.",
    "Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan.",
    "INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France.",
    "Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.",
    "Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy.",
    "Division of Hematology and Oncology, Vanderbilt Ingram Cancer Center and Vanderbilt University School of Medicine, Nashville, TN.",
    "Haematology Department, University Hospital Vall d'Hebron, Barcelona, Spain.",
    "Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.",
    "Hematology and Oncology Department, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.",
    "Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.",
    "Division of General Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.",
    "Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.",
    "Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yu-Hung Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Dorothée Selimoglu-Buet",
      "orcid": "0000-0002-3565-2709"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Carmelo Gurnari"
    },
    {
      "affs": [
        6
      ],
      "name": "Matthew T Villaume"
    },
    {
      "affs": [
        6
      ],
      "name": "Somedeb Ball"
    },
    {
      "affs": [
        3
      ],
      "name": "Nathalie Droin",
      "orcid": "0000-0002-6099-5324"
    },
    {
      "affs": [
        4
      ],
      "name": "Hussein Awada"
    },
    {
      "affs": [
        7
      ],
      "name": "Andres Jerez"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Andrius Zucenka"
    },
    {
      "affs": [
        1,
        10
      ],
      "name": "Chi-Yuan Yao"
    },
    {
      "affs": [
        1,
        10
      ],
      "name": "Chien-Chin Lin"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Hsin-An Hou"
    },
    {
      "affs": [
        1,
        10
      ],
      "name": "Wen-Chien Chou"
    },
    {
      "affs": [
        1,
        13
      ],
      "name": "Hwei-Fang Tien"
    },
    {
      "affs": [
        4
      ],
      "name": "Jaroslaw P Maciejewski"
    },
    {
      "affs": [
        6
      ],
      "name": "Michael R Savona"
    },
    {
      "affs": [
        3
      ],
      "name": "Eric Solary"
    },
    {
      "affs": [
        0
      ],
      "name": "Kiran Batta"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel H Wiseman",
      "orcid": "0000-0003-0715-1402"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3gvbndm3jeb8c.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bneo.2026.100286",
  "fulltext_url": "https://europepmc.org/articles/PMC13681982",
  "id": "3gvbndm3jeb8c",
  "issns": [
    "2950-3280"
  ],
  "landing_url": "https://europepmc.org/article/MED/42904085",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7202350635",
  "pdf_url": "https://europepmc.org/articles/PMC13681982?pdf=render",
  "pmcid": "PMC13681982",
  "pmid": "42904085",
  "published": "2026-08-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3gvbndm3jeb8c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42904085",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42904085"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Acute Myeloid Leukemia Research",
      "subfield": "general"
    }
  ],
  "title": "Prognostic implications of TET2 variant allele frequency in chronic myelomonocytic leukemia: a multicenter study.",
  "title_text": "Prognostic implications of TET2 variant allele frequency in chronic myelomonocytic leukemia: a multicenter study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/3gvbndm3jeb8c",
  "venue": "Blood neoplasia",
  "versions": []
}