{"entity": "publication", "iuid": "96e40f0e3f1e469e8f39ed47c75492f7", "timestamp": "2026-07-17T17:24:04.693Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/96e40f0e3f1e469e8f39ed47c75492f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/96e40f0e3f1e469e8f39ed47c75492f7"}}, "title": "Ontogeny-specific induction of the KMT2A::AFF1-fusion drives development of a distinct CD24 positive pre-leukemic state.", "authors": [{"family": "Calder\u00f3n", "given": "Ariana S", "initials": "AS", "orcid": "0000-0001-6271-6256", "researcher": {"href": "https://publications.scilifelab.se/researcher/67a972ca632a414f8d82013f69af6d15.json"}}, {"family": "Ghazanfari", "given": "Roshanak", "initials": "R"}, {"family": "Masoumi", "given": "Zahra", "initials": "Z"}, {"family": "Kharazi", "given": "Shabnam", "initials": "S"}, {"family": "Palo", "given": "Sara", "initials": "S"}, {"family": "Lang", "given": "Stefan", "initials": "S", "orcid": "0000-0002-0854-2328", "researcher": {"href": "https://publications.scilifelab.se/researcher/eed2cc9c00a7404d9cd4821a7d0cd92d.json"}}, {"family": "\u017demaitis", "given": "Kristijonas", "initials": "K"}, {"family": "Eldeeb", "given": "Mohamed", "initials": "M", "orcid": "0000-0002-8636-2189", "researcher": {"href": "https://publications.scilifelab.se/researcher/00a89e30b4ba4216ae5a9ca189fd8da0.json"}}, {"family": "Subramaniam", "given": "Agatheeswaran", "initials": "A", "orcid": "0000-0003-3966-3875", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ccb1e6798b84f128c3143c8da8bd35a.json"}}, {"family": "Soneji", "given": "Shamit", "initials": "S"}, {"family": "Stam", "given": "Ronald W", "initials": "RW", "orcid": "0000-0003-4986-1656", "researcher": {"href": "https://publications.scilifelab.se/researcher/f528aaa6b3ba479f85619e1496e3f395.json"}}, {"family": "Bryder", "given": "David", "initials": "D", "orcid": "0000-0002-8761-4237", "researcher": {"href": "https://publications.scilifelab.se/researcher/30133810251344cb9fa3e42f0e2fd511.json"}}, {"family": "B\u00f6iers", "given": "Charlotta", "initials": "C", "orcid": "0000-0002-4876-1218", "researcher": {"href": "https://publications.scilifelab.se/researcher/e33b5ec83be045c693675ab6bda2e9d0.json"}}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "39", "issue": "9", "pages": "2099-2111", "issn-l": "0887-6924"}, "abstract": "Infant Acute Lymphoblastic Leukemia (ALL) driven by the KMT2A::AFF1 onco-fusion is an aggressive, poor prognosis disease with few co-operative mutations. The fusion originates in utero, yet the embryonic initiating steps of disease development remain poorly understood. Here, we present a novel murine KMT2A::AFF1 model, that provides key insights into KMT2A::AFF1 pre-leukemia, relevant to human disease. The model enables precise oncogene induction, and upon targeting hematopoietic stem and progenitor cells (HSPCs) a selective negative impact on proliferation of hematopoietic stem cells (HSCs) was observed, regardless of developmental state during induction. However, a unique CD24+PreProB subset expanded exclusively within the KMT2A::AFF1 embryonic context. This population was absent when targeting lymphoid progenitors, highlighting the importance of the cell of origin for leukemic development. The CD24+PreProB subset displayed key features of pre-leukemic stem cells, including lineage plasticity and aberrant engraftment ability. In line with their pre-malignant phenotype, single-cell transcriptomics revealed a signature consistent with stemness, and notable, up-regulation of Hmga2, a regulator of self-renewal. The signature was critically transferable to human KMT2A::AFF1 patients. Furthermore, given that CD24 is a potential therapeutic target, our findings uncover a distinct embryonic pre-leukemic state with direct relevance to human disease.", "doi": "10.1038/s41375-025-02665-9", "pmid": "40646135", "labels": {"Clinical Genomics Lund": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12380613"}, {"db": "pii", "key": "10.1038/s41375-025-02665-9"}], "notes": [], "created": "2025-11-05T18:41:18.358Z", "modified": "2025-11-10T14:06:52.558Z"}