{"entity": "researcher", "timestamp": "2026-08-20T20:37:13.356Z", "family": "Lundin", "given": "Vanessa", "initials": "V", "orcid": "0000-0003-2335-3370", "affiliations": ["Center for Hematology and Regenerative Medicine, Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b746851c7044c7f8563cc39ed9f457e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b746851c7044c7f8563cc39ed9f457e"}}, "publications": [{"entity": "publication", "iuid": "4fa302a131c347a4967d5d96e978a559", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/4fa302a131c347a4967d5d96e978a559.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/4fa302a131c347a4967d5d96e978a559"}}, "title": "SF3B1-mutant models of RNA mis-splicing uncover UBA1 as a therapeutic target in myelodysplastic neoplasms.", "authors": [{"family": "Thier", "given": "Jonas", "initials": "J", "orcid": "0009-0007-5226-0372", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2670901806e94464820ea6749c625a41.json"}}, {"family": "Hofmann", "given": "Sophia", "initials": "S", "orcid": "0009-0006-6625-8348", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5299df88b9d04e93b39f5a2ec32f4e26.json"}}, {"family": "Kirchhof", "given": "Katharina M", "initials": "KM", "orcid": "0000-0001-8412-4585", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6fd0174077664b6c94b948c4b6f97346.json"}}, {"family": "Todisco", "given": "Gabriele", "initials": "G", "orcid": "0000-0001-6583-3829", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/769f70d382bc46cfbfffa0b5cd16710f.json"}}, {"family": "Mortera-Blanco", "given": "Teresa", "initials": "T", "orcid": "0000-0002-8399-1430", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2afa2c9bceb44bd7aa4810e7846b5607.json"}}, {"family": "Lilienthal", "given": "Ingrid", "initials": "I", "orcid": "0000-0001-5270-7268", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5831c58c547d47f9826997c52763a30b.json"}}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/14307e4299ce40a49d2e45265398676c.json"}}, {"family": "Barbosa", "given": "Indira", "initials": "I", "orcid": "0009-0004-1171-2932", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2c92d74875a9433fafc001f47e3f48c3.json"}}, {"family": "Bj\u00f6rklund", "given": "Ann-Charlotte", "initials": "AC", "orcid": "0009-0008-3745-503X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2646432d278e40b79a75cbb5222ceb39.json"}}, {"family": "Deslauriers", "given": "Andr\u00e9 G", "initials": "AG", "orcid": "0000-0002-2854-5681", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2bcb1a0e3ce6438ab3aec7e24a383d3a.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/749eedaa5f69414aa315bb875eef9475.json"}}, {"family": "Papaemmanuil", "given": "Elli", "initials": "E", "orcid": "0000-0003-1709-8983", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6ea61c4aa9324a398fffe747c0e7824d.json"}}, {"family": "Papapetrou", "given": "Eirini P", "initials": "EP", "orcid": "0000-0001-7002-417X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7951631751334226bc25259c6af73da8.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E", "orcid": "0000-0002-7839-3743", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/66eecd3e3886496cb7f7dcaefa5e6a36.json"}}, {"family": "Moura", "given": "Pedro L", "initials": "PL", "orcid": "0000-0002-0493-5394", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ac418bab887f4153b20d77dfc455b3a7.json"}}, {"family": "Lundin", "given": "Vanessa", "initials": "V", "orcid": "0000-0003-2335-3370", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b746851c7044c7f8563cc39ed9f457e.json"}}], "type": "journal article", "published": "2025-11-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "39", "issue": "11", "pages": "2801-2811", "issn-l": "0887-6924"}, "abstract": "Myelodysplastic syndromes with somatic mutations in the splicing factor SF3B1 gene (MDS-SF3B1) result in RNA mis-splicing, erythroid dysplasia and ultimately refractory anemia. Precision medicine approaches for MDS-SF3B1 remain challenging due to both the complexity of the mis-splicing landscape and its evaluation in disease-accurate models. To uncover novel RNA mis-splicing events, isogenic SF3B1K700E and SF3B1WT iPSC lines from an MDS-SF3B1 patient were differentiated into hematopoietic cells and analyzed via unsupervised splicing event profiling using full-length RNA sequencing. This identified SF3B1K700E-specific mis-splicing of ubiquitin-like modifier activating enzyme 1 (UBA1), which encodes a key E1 protein at the apex of the ubiquitination cascade. UBA1 mis-splicing (UBA1ms) introduced protein instability and decreased total UBA1 levels, rendering mutated cells susceptible to the small-molecule UBA1 inhibitor TAK-243. Analysis of CD34+ RNA sequencing data from an MDS patient cohort confirmed unique and ubiquitous UBA1ms in MDS-SF3B1 patients, absent in other splicing factor-mutated MDS cases or healthy controls. TAK-243 selectively targeted MDS-SF3B1 primary CD34+ cells and reduced mutant cell numbers in colony-forming assays. In contrast, normal hematopoietic progenitor cells were unaffected. Altogether, we here define UBA1ms as a novel therapeutic vulnerability in SF3B1-mutant cells, introducing UBA1 inhibition as a potential avenue for future MDS-SF3B1 treatments.", "doi": "10.1038/s41375-025-02740-1", "pmid": "40858805", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12589102"}, {"db": "pii", "key": "10.1038/s41375-025-02740-1"}], "notes": [], "created": "2026-08-20T08:47:24.962Z", "modified": "2026-08-20T08:47:51.017Z"}, {"entity": "publication", "iuid": "656e0d93c4f0445caf2ce7d562d50b2b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/656e0d93c4f0445caf2ce7d562d50b2b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/656e0d93c4f0445caf2ce7d562d50b2b"}}, "title": "The clinical phenotype of germline RUNX1 mutations in relation to the accompanying somatic variants and RUNX1 isoform expression.", "authors": [{"family": "Cabrerizo Granados", "given": "David", "initials": "D"}, {"family": "Barbosa", "given": "Indira", "initials": "I"}, {"family": "Baliakas", "given": "Panagiotis", "initials": "P"}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E"}, {"family": "Lundin", "given": "Vanessa", "initials": "V", "orcid": "0000-0003-2335-3370", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b746851c7044c7f8563cc39ed9f457e.json"}}], "type": "journal article", "published": "2023-11-00", "journal": {"title": "Genes Chromosomes Cancer", "issn": "1098-2264", "volume": "62", "issue": "11", "pages": "672-677", "issn-l": "1045-2257"}, "abstract": "Germline RUNX1 mutations lead to familial platelet disorder with associated myeloid malignancy (FPDMM), characterized by thrombocytopenia, abnormal bleeding, and an elevated risk of developing myelodysplastic neoplasia (MDS) and acute myeloid leukemia (AML) at young age. However, it is not known why or how germline carriers of RUNX1 mutations have a particular propensity to develop myeloid hematologic malignancies, but the acquisition and composition of somatic mutations are believed to initiate and determine disease progression. We present a novel family pedigree that shares a common germline RUNX1R204* variant and exhibits a spectrum of somatic mutations and related myeloid malignancies (MM). RUNX1 mutations are associated with inferior clinical outcome; however, the proband of this family developed MDS with ring sideroblasts (MDS-RS), classified as a low-risk MDS subgroup. His relatively indolent clinical course is likely due to a specific somatic mutation in the SF3B1 gene. While the three main RUNX1 isoforms have been ascribed various roles in normal hematopoiesis, they are now being increasingly recognized as involved in myeloid disease. We investigated the RUNX1 transcript isoform patterns in the proband and his sister, who carries the same germline RUNX1R204* variant, and has FPDMM but no MM. We demonstrate a RUNX1a increase in MDS-RS, as previously reported in MM. Interestingly, we identify a striking unbalance of RUNX1b and -c in FPDMM. In conclusion, this report reinforces the relevance of somatic variants on the clinical phenotypic heterogeneity in families with germline RUNX1 deficiency and investigates a potential new role for RUNX1 isoform disequilibrium as a mechanism for development of MM.", "doi": "10.1002/gcc.23184", "pmid": "37303296", "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T06:32:55.953Z", "modified": "2026-08-20T06:32:56.045Z"}]}