{
  "abstract": "Variable risks of acute myeloid leukemia (AML) progression of myeloid malignancies are dependent upon their mutational and clinical features. A common TCL1A gene promoter polymorphism (rs2887399-T allele, G/T or T/T) reduces TCL1A expression and fitness for expansion of TCL1A-linked mutations recurrently found in MDS and CMML (TET2, ASXL1, SF3B1, SRSF2, IDH1/2, JAK2) compared to those with the G/G-allele (wild type). We analyzed 208 MDS and CMML patients who underwent targeted next generation sequencing of myeloid malignancy genes and rs2887399 genotyping. Primary analysis for evaluating AML-progression-free survival (PFS) and the cumulative incidence of AML progression compared patients with TCL1A-linked mutations plus the rs2887399-T allele to those with these mutations plus the wild type rs2887399-G/G genotype. Among patients with TCL1A-linked mutations (119/208, 57%), rs2887399-T carriers (n = 35) had lower 3-year AML progression (2.9% vs 18%, p = .037), longer AML PFS (96.4% vs 79.8%, P = .039) and lower cumulative incidence of AML (2.9% vs 17.3%, P = .006) than G/G carriers (n = 84), despite similar molecular risk. Multivariable Cox analysis showed reduced AML progression hazard in TCL1A-linked rs2887399-T carriers versus the TCL1A-linked-G/G and non-TCL1A-linked-T (HR 0.26, 95% CI 0.06-0.88, p=0.029). In conclusion, the rs2887399-T allele diminished and delayed AML evolution in MDS/CMML patients with TCL1A-linked mutations. These data support the concept that the TCL1A polymorphism in the setting of specific somatic mutations is a modulator of leukemogenesis, providing potential utility of such germline genotyping for disease risk stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Hematology Division, Department of Medicine, Stanford University School of Medicine, Stanford, CA",
    "Department of Pathology, Stanford University School of Medicine, Stanford, CA",
    "Quantitative Sciences Unit, Stanford University, Stanford, CA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alfonso Molina"
    },
    {
      "affs": [
        1
      ],
      "name": "Jayakrishnan Gopakumar"
    },
    {
      "affs": [
        2
      ],
      "name": "Alexandria Jensen"
    },
    {
      "affs": [
        0
      ],
      "name": "Vishesh Khanna"
    },
    {
      "affs": [
        1
      ],
      "name": "Henning Stehr"
    },
    {
      "affs": [
        1
      ],
      "name": "Siddhartha Jaiswal"
    },
    {
      "affs": [
        0
      ],
      "name": "Peter L. Greenberg"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5znf3p6hvqx6r.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bneo.2026.100290",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718587/?tool=EBI",
  "id": "5znf3p6hvqx6r",
  "issns": [
    "2950-3280"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13718587",
  "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": [
    [
      "heading",
      "Myeloid Neoplasia"
    ],
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W4417007298",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718587/pdf/?tool=EBI",
  "pmcid": "PMC13718587",
  "pmid": "42959877",
  "published": "2026-08-24",
  "publisher": "The American Society of Hematology",
  "ris": "https://research.draconitic.com/paper/5znf3p6hvqx6r.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:39Z",
      "native_id": "PMC:PMC13718587",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13718587"
    },
    {
      "first_seen": "2026-10-31T12:21:46Z",
      "native_id": "MED:42959877",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42959877"
    },
    {
      "first_seen": "2026-11-02T12:22:35Z",
      "native_id": "PMC13718587",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.bneo.2026.100290"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Acute Myeloid Leukemia Research",
      "subfield": "general"
    }
  ],
  "title": "TCL1A polymorphism predicts AML progression in myeloid neoplasms",
  "title_text": "TCL1A polymorphism predicts AML progression in myeloid neoplasms",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:35Z",
  "url": "https://research.draconitic.com/paper/5znf3p6hvqx6r",
  "venue": "Blood neoplasia",
  "versions": []
}