{"entity": "researcher", "timestamp": "2026-08-20T20:54:36.757Z", "family": "Papapetrou", "given": "Eirini P", "initials": "EP", "orcid": "0000-0001-7002-417X", "affiliations": ["Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.", "Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.", "Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA.", "Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.", "Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/7951631751334226bc25259c6af73da8.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/7951631751334226bc25259c6af73da8"}}, "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"}]}