{
  "abstract": "Despite widespread immunophenotyping in acute myeloid leukemia (AML), its immunophenotypic heterogeneity remains incompletely understood. Here, we applied state-of-the-art computational modeling to >50 million single cells from diagnostic bone marrow aspirates of 502 AML patients. Jointly modeling leukemic and non-malignant cells, we identified seven patient clusters with distinct immunophenotypic signatures. These clusters showed strong concordance with recurrent mutations, including NPM1, IDH1/IDH2, CEBPA, and t(8;21)(q22;q22); RUNX1-RUNX1T1 fusions, and enabled accurate prediction of genomic subgroups. Although these immunophenotypic signatures were not associated with therapy responses, loss of HLA-DR expression on leukemic blasts at diagnosis was independently associated with inferior outcomes in patients with chromatin-spliceosome mutations. In addition, we identified an immunophenotypic patient cluster comprising ∼11% of patients characterized by significant bone marrow lymphocyte enrichment where outcomes diverged depending on genetic risk. Together, these findings provide a comprehensive single-cell characterization of AML bone marrow and reveal clinically relevant genotype-phenotype relationships.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "name": "Tim R. Mocking",
      "orcid": "0000-0001-9170-4131"
    },
    {
      "name": "Tom Reuvekamp",
      "orcid": "0009-0001-1346-6606"
    },
    {
      "name": "Lukas H. Haaksma",
      "orcid": "0009-0008-2179-4870"
    },
    {
      "name": "Eirini Papavasileiou",
      "orcid": "0009-0001-6249-6262"
    },
    {
      "name": "Angèle Kelder"
    },
    {
      "name": "Willemijn J. Scholten"
    },
    {
      "name": "Dimitri A. Breems"
    },
    {
      "name": "Thomas Fischer"
    },
    {
      "name": "Bjørn T. Gjertsen",
      "orcid": "0000-0001-9358-9704"
    },
    {
      "name": "Laimonas Griškevičius"
    },
    {
      "name": "Gunnar Juliusson"
    },
    {
      "name": "Johan A. Maertens"
    },
    {
      "name": "Markus G. Manz",
      "orcid": "0000-0002-4676-7931"
    },
    {
      "name": "Thomas Pabst"
    },
    {
      "name": "Jakob R. Passweg",
      "orcid": "0000-0001-7092-3351"
    },
    {
      "name": "Kimmo Porkka"
    },
    {
      "name": "Jeroen J.W.M. Janssen"
    },
    {
      "name": "Patrycja Gradowska"
    },
    {
      "name": "Bob Löwenberg"
    },
    {
      "name": "Gert J. Ossenkoppele"
    },
    {
      "name": "Arjan A. van de Loosdrecht"
    },
    {
      "name": "David C. de Leeuw",
      "orcid": "0000-0003-4591-8467"
    },
    {
      "name": "Jacqueline Cloos"
    },
    {
      "name": "Peter J.M. Valk"
    },
    {
      "name": "Costa Bachas",
      "orcid": "0000-0001-5983-6193"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3qx8pyvk9yg04.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117762",
  "fulltext_url": "https://europepmc.org/articles/PMC13682389",
  "id": "3qx8pyvk9yg04",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03143-3",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Health sciences"
    ],
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7221555811",
  "pdf_url": "https://europepmc.org/articles/PMC13682389?pdf=render",
  "pmcid": "PMC13682389",
  "pmid": "42903857",
  "published": "2026-10-12",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/3qx8pyvk9yg04.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.1016/j.isci.2026.117762",
      "source": "feed-cell",
      "url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03143-3"
    },
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1016/j.isci.2026.117762",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2589004226031433"
    },
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42903857",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903857"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Acute Myeloid Leukemia Research",
      "subfield": "general"
    }
  ],
  "title": "The immunophenotypic landscape of newly diagnosed acute myeloid leukemia: Associations with genotype and outcomes",
  "title_text": "The immunophenotypic landscape of newly diagnosed acute myeloid leukemia: Associations with genotype and outcomes",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/3qx8pyvk9yg04",
  "venue": "iScience",
  "versions": []
}