{
  "abstract": "Lineage switch (LS) is a rare but aggressive immunophenotypic transformation of acute leukemia associated with limited therapeutic options and poor clinical outcome. Although LS has been increasingly recognized in the era of CD19‐directed immunotherapies, its biological basis remains incompletely understood. Most reported pediatric LS cases occur in KMT2A‐rearranged (KMT2A‐r) leukemia, highlighting a link between developmental origin and lineage plasticity. In this review, we provide a comprehensive overview of the clinical, molecular, epigenetic, and cellular determinants of pediatric LS. We systematically reviewed the literature and identified 201 pediatric LS cases reported between 1994 and 2026. Among these, 70.1% involved B‐lymphoblastic leukemias switching to acute myeloid leukemias, with KMT2A‐r (47.8%) and DUX4‐rearranged (14.9%) leukemias representing the most frequent genetic subtypes. Across the published cases, LS occurred earlier following blinatumomab exposure than after chimeric antigen receptor cells or chemotherapy alone. We discuss current mechanistic concepts underlying LS, including epigenetic remodeling, chromatin regulation, developmental programs, the cell‐of‐origin, and therapy‐associated selective pressures that promote lineage plasticity. By integrating clinical evidence with current insights into leukemia biology, this review provides a framework for understanding LS in pediatric leukemias and highlights priorities for future research, early detection, and development of preventive and/or therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Paediatrics University of Oxford Oxford United Kingdom",
    "Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty Heinrich Heine University Düsseldorf Düsseldorf Germany",
    "MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine University of Oxford Oxford United Kingdom",
    "Department of Haematology Great Ormond Street Hospital for Children London United Kingdom"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Katharina Daugs",
      "orcid": "0009-0006-1123-893X"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Prazmo"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Anindita Roy",
      "orcid": "0000-0001-8607-5748"
    },
    {
      "affs": [
        1
      ],
      "name": "Arndt Borkhardt",
      "orcid": "0000-0002-6121-4737"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5fgk8zfdnbjef.bib",
  "cited_by": 0,
  "doi": "10.1002/hem3.70528",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733654/",
  "id": "5fgk8zfdnbjef",
  "issns": [
    "2572-9241"
  ],
  "landing_url": "https://doi.org/10.1002/hem3.70528",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review Article"
    ],
    [
      "openalex",
      "2720|Acute Lymphoblastic Leukemia research"
    ]
  ],
  "openalex": "W7225263485",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hem3.70528",
  "pmcid": "PMC13733654",
  "pmid": "42985693",
  "published": "2026-11-04",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/5fgk8zfdnbjef.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:22Z",
      "native_id": "PMC13733654",
      "source": "pmc",
      "url": "https://doi.org/10.1002/hem3.70528"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Acute Lymphoblastic Leukemia research",
      "subfield": "general"
    }
  ],
  "title": "Lineage switch in childhood leukemia",
  "title_text": "Lineage switch in childhood leukemia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:22Z",
  "url": "https://research.draconitic.com/paper/5fgk8zfdnbjef",
  "venue": "HemaSphere",
  "versions": []
}