{
  "abstract": "Background: Acute myeloid leukemia (AML) is characterized by substantial biological heterogeneity that is incompletely captured by current risk-classification frameworks. Podocalyxin-like 2 (PODXL2), a CD34-family transmembrane sialomucin implicated in tumor progression in solid tumors, remains poorly characterized in AML. Methods: We conducted integrated clinical, genomic, transcriptomic, regulatory network, and ex vivo drug-response analyses using two independent AML cohorts, TCGA-LAML and BeatAML. Results: Elevated PODXL2 expression was consistently associated with inferior overall survival across both cohorts, including after adjustment for established clinical risk factors. PODXL2-high AML was enriched for adverse-risk features, including ELN 2022 adverse-risk classification, poor-risk cytogenetics, and TP53 mutations, whereas IDH2 mutations were more frequent in PODXL2-low AML. Transcriptomic analyses identified a distinct PODXL2-high state characterized by enrichment of MYC and E2F target programs, cell-cycle progression, DNA repair, oxidative phosphorylation, mTORC1 signaling, and metabolic pathways. Regulatory network analyses demonstrated enhanced MYC/E2F-associated regulatory activity. PODXL2-high AML also exhibited altered differentiation-state features, characterized by reduced representation of monocyte-like and conventional dendritic cell-like malignant cell states. Ex vivo drug-response profiling identified distinct PODXL2-associated response patterns, including reduced sensitivity to OTX-015 and SRC-family kinase inhibitors. Conclusions: PODXL2 expression is associated with adverse clinical and molecular features, distinct transcriptional programs, altered differentiation states, and differential ex vivo drug-response patterns in AML. These findings identify PODXL2 expression as a marker associated with adverse clinical and molecular features and inferior survival in AML, although its prognostic discrimination as a standalone marker is modest. Further functional and prospective studies are warranted to establish its biological and clinical significance.",
  "abstract_shown": true,
  "affiliations": [
    "School of Medicine, LSU Health Science Center, New Orleans, LA 70112, USA",
    "Department of Microbiology, Genetics and Immunology, LSU LCMC Health Cancer Center, New Orleans, LA 70112, USA",
    "Department of Interdisciplinary Oncology, LSU LCMC Health Cancer Center, New Orleans, LA 70112, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hyun Min Ko"
    },
    {
      "affs": [
        0
      ],
      "name": "Katherine Scarton"
    },
    {
      "affs": [
        0
      ],
      "name": "Samantha C. Covey"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lucio Miele",
      "orcid": "0000-0002-5853-7287"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Sun Young Kim",
      "orcid": "0009-0009-5743-9683"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3jrw7mgvnjaft.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18193219",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664358/?tool=EBI",
  "id": "3jrw7mgvnjaft",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13664358",
  "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",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7220724313",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664358/pdf/?tool=EBI",
  "pmcid": "PMC13664358",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/3jrw7mgvnjaft.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "PMC:PMC13664358",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13664358"
    },
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18193219",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/19/3219"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6694",
      "subfield": "oncology"
    }
  ],
  "title": "PODXL2 Expression Is Associated with Inferior Survival, Adverse-Risk Features, and Distinct Transcriptional Programs in Acute Myeloid Leukemia",
  "title_text": "PODXL2 Expression Is Associated with Inferior Survival, Adverse-Risk Features, and Distinct Transcriptional Programs in Acute Myeloid Leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:58Z",
  "url": "https://research.draconitic.com/paper/3jrw7mgvnjaft",
  "venue": "Cancers",
  "versions": []
}