{"entity": "researcher", "timestamp": "2026-09-26T00:40:22.874Z", "family": "Langerak", "given": "Anton W", "initials": "AW", "orcid": "0000-0002-2078-3220", "affiliations": ["Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/535a658cf9db4176b46671be08e4f909.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/535a658cf9db4176b46671be08e4f909"}}, "publications": [{"entity": "publication", "iuid": "74729dc65e004ac79d33f36fce0ed5ba", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/74729dc65e004ac79d33f36fce0ed5ba.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/74729dc65e004ac79d33f36fce0ed5ba"}}, "title": "Disease-specific U1 spliceosomal RNA mutations in mature B-cell neoplasms.", "authors": [{"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": "0000-0003-2910-9440", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50c437deb106439282f36834216b320a.json"}}, {"family": "Shuai", "given": "Shimin", "initials": "S", "orcid": "0000-0002-9527-8018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3896d0cb0c3b4d0fb8b34e39e654428c.json"}}, {"family": "Clot", "given": "Guillem", "initials": "G", "orcid": "0000-0003-2588-7413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ff9667b5750841499b2cddfa2aba3294.json"}}, {"family": "Hilton", "given": "Laura K", "initials": "LK", "orcid": "0000-0002-6413-6586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f06e235a0e1b40c68e292ef5420ed157.json"}}, {"family": "Diaz-Navarro", "given": "Ander", "initials": "A"}, {"family": "Mart\u00edn", "given": "Silvia", "initials": "S"}, {"family": "Royo", "given": "Romina", "initials": "R"}, {"family": "Baumann", "given": "Tycho", "initials": "T"}, {"family": "Kulis", "given": "Marta", "initials": "M"}, {"family": "L\u00f3pez-Oreja", "given": "Irene", "initials": "I"}, {"family": "Cossio", "given": "Manuel", "initials": "M"}, {"family": "Lu", "given": "Junyan", "initials": "J", "orcid": "0000-0002-9211-0746", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d6b5e8ff9f04ebc97f0086446bb2a95.json"}}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Young", "given": "Emma", "initials": "E"}, {"family": "Plevova", "given": "Karla", "initials": "K", "orcid": "0000-0002-6148-8877", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a4174bc21ce468a90d6f7cba6688179.json"}}, {"family": "Knisbacher", "given": "Binyamin A", "initials": "BA"}, {"family": "Lin", "given": "Ziao", "initials": "Z"}, {"family": "Hahn", "given": "Cynthia K", "initials": "CK"}, {"family": "Bousquets", "given": "Pablo", "initials": "P", "orcid": "0000-0002-2969-008X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e649e6efb5b4b55b52b0846ca125be2.json"}}, {"family": "Alcoceba", "given": "Miguel", "initials": "M", "orcid": "0000-0002-3819-4846", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30856cb02a2f46e6a4a4ee435dd985ee.json"}}, {"family": "Gonz\u00e1lez", "given": "Marcos", "initials": "M"}, {"family": "Colado", "given": "Enrique", "initials": "E", "orcid": "0000-0001-8675-8207", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/69bc9ef7e1db420ba922b82cc9992ae9.json"}}, {"family": "Payer", "given": "\u00c1ngel R", "initials": "\u00c1R"}, {"family": "Aymerich", "given": "Marta", "initials": "M"}, {"family": "Terol", "given": "Mar\u00eda J", "initials": "MJ"}, {"family": "Rivas-Delgado", "given": "Alfredo", "initials": "A"}, {"family": "Enjuanes", "given": "Anna", "initials": "A"}, {"family": "Ruiz-Gasp\u00e0", "given": "S\u00edlvia", "initials": "S"}, {"family": "Chatzikonstantinou", "given": "Thomas", "initials": "T", "orcid": "0000-0003-4105-1253", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a205228c1594457fbd55004721eb19c3.json"}}, {"family": "H\u00e4gerstrand", "given": "Daniel", "initials": "D", "orcid": "0000-0001-7270-0776", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c3221dc6f79b4d77bea303ab5e2b6fd2.json"}}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "Skaftason", "given": "Aron", "initials": "A"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Stranska", "given": "Kamila", "initials": "K", "orcid": "0000-0001-7678-1163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e117c63824743888c475df6b819f05f.json"}}, {"family": "Doubek", "given": "Michael", "initials": "M", "orcid": "0000-0002-1269-6282", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/69820fa805ac43ad892da50ac25d3e72.json"}}, {"family": "van Gastel-Mol", "given": "Ellen J", "initials": "EJ"}, {"family": "Davis", "given": "Zadie", "initials": "Z"}, {"family": "Walewska", "given": "Renata", "initials": "R"}, {"family": "Scarf\u00f2", "given": "Lydia", "initials": "L", "orcid": "0000-0002-0844-0989", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7697d7b279ae48a387843c617f30fa3c.json"}}, {"family": "Trentin", "given": "Livio", "initials": "L", "orcid": "0000-0003-1222-6149", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/820ab4c1a5534ada88d9c318fa8aa2e1.json"}}, {"family": "Visentin", "given": "Andrea", "initials": "A", "orcid": "0000-0003-0271-7200", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/10a25bb174034d55a6a2f0fccb036f02.json"}}, {"family": "Parikh", "given": "Sameer A", "initials": "SA", "orcid": "0000-0002-3221-7314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a88ede10daa4046aa907682e1b8f8b8.json"}}, {"family": "Rabe", "given": "Kari G", "initials": "KG", "orcid": "0000-0002-7313-1875", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ffc22e22bdfd4d85bb699236989449cf.json"}}, {"family": "Moia", "given": "Riccardo", "initials": "R", "orcid": "0000-0001-7393-1138", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35dc8f45c11b4d58999560cc83911a5e.json"}}, {"family": "Armand", "given": "Marine", "initials": "M", "orcid": "0000-0001-8906-3128", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4076e069779745059ba33556a6f4b295.json"}}, {"family": "Rossi", "given": "Davide", "initials": "D"}, {"family": "Davi", "given": "Frederic", "initials": "F"}, {"family": "Gaidano", "given": "Gianluca", "initials": "G", "orcid": "0000-0002-4681-0151", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c61a087170e49ae9f062617c751153e.json"}}, {"family": "Kay", "given": "Neil E", "initials": "NE", "orcid": "0000-0002-5951-5055", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8ed8e38f552b44c28e3a32023c07b537.json"}}, {"family": "Shanafelt", "given": "Tait D", "initials": "TD"}, {"family": "Ghia", "given": "Paolo", "initials": "P", "orcid": "0000-0003-3750-7342", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/475d35f1a3c446819b2f24be819c2dee.json"}}, {"family": "Oscier", "given": "David", "initials": "D"}, {"family": "Langerak", "given": "Anton W", "initials": "AW", "orcid": "0000-0002-2078-3220", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/535a658cf9db4176b46671be08e4f909.json"}}, {"family": "Be\u00e0", "given": "S\u00edlvia", "initials": "S", "orcid": "0000-0001-7192-2385", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/11db86f06c3340878b764b6d3ae9ecf0.json"}}, {"family": "L\u00f3pez-Guillermo", "given": "Armando", "initials": "A"}, {"family": "Neuberg", "given": "Donna", "initials": "D", "orcid": "0000-0003-2566-3145", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/70b2f9e23251469987cbe7b42d38dc58.json"}}, {"family": "Wu", "given": "Catherine J", "initials": "CJ", "orcid": "0000-0002-3348-5054", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d71b7e5cfa1c49d994df22a9a9657686.json"}}, {"family": "Getz", "given": "Gad", "initials": "G", "orcid": "0000-0002-0936-0753", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc65099492394065bb61f94c89425aa3.json"}}, {"family": "Pospisilova", "given": "Sarka", "initials": "S", "orcid": "0000-0001-7136-2680", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/75467f2097fe4bcfb274e40e46cfbf12.json"}}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K", "orcid": "0000-0001-8529-640X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f6107d6f774ee6acb2c66ecfcb90cc.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc038c13a8cb44bd93f3552ed250a179.json"}}, {"family": "Huber", "given": "Wolfgang", "initials": "W"}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13160825496147c897b8d57be3a61caa.json"}}, {"family": "Colomer", "given": "Dolors", "initials": "D", "orcid": "0000-0001-7486-8484", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e7b74af349aa4e269efeaa45181afeb6.json"}}, {"family": "Mart\u00edn-Subero", "given": "Jos\u00e9 I", "initials": "JI", "orcid": "0000-0001-8809-5195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6b1944a98214848b864342473012567.json"}}, {"family": "Delgado", "given": "Julio", "initials": "J", "orcid": "0000-0002-5157-4376", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c8bb41dc1fdf4709b6c193df84127af8.json"}}, {"family": "Morin", "given": "Ryan D", "initials": "RD", "orcid": "0000-0003-2932-7800", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f6f69a934a0a40faa7939021e304276d.json"}}, {"family": "Stein", "given": "Lincoln D", "initials": "LD"}, {"family": "Puente", "given": "Xose S", "initials": "XS", "orcid": "0000-0001-9525-1483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/682af7b4d9624247b095cb285b54a4c0.json"}}, {"family": "Campo", "given": "El\u00edas", "initials": "E", "orcid": "0000-0001-9850-9793", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ab2ad72e7442da10e441a24100503.json"}}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "39", "issue": "9", "pages": "2076-2086", "issn-l": "0887-6924"}, "abstract": "Recurrent mutations in the third base of U1 spliceosomal RNA responsible for marked splicing and expression abnormalities have been described in chronic lymphocytic leukemia (CLL) and some solid tumors. However, the clinical significance of these mutations in large and independent CLL cohorts as well as their presence in other B-cell neoplasms is unknown. Here we characterized U1 mutations in 1670 CLL and 363 mature B-cell lymphomas. We confirmed that the g.3A>C U1 mutation is found in 3.5% of CLL, which conferred rapid disease progression independently of the main biological and clinical prognostic markers of the disease. Additionally, a recurrent g.9C>T mutation was found in 1.5% of CLL causing downstream splicing alterations and associated with adverse prognosis. We also identified a g.4C>T mutation in 10% of diffuse large B-cell lymphomas of the germinal center subtype and a g.7A>G mutation in 30% of EBV-negative Burkitt lymphomas, both of which altered the splicing pattern of multiple genes. This study reveals novel, recurrent, and tumor-specific U1 mutations in mature B-cell neoplasms with biological and prognostic implications, thus establishing U1 as a novel pan-B-cell malignancy driver gene.", "doi": "10.1038/s41375-025-02667-7", "pmid": "40588565", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12380619"}, {"db": "pii", "key": "10.1038/s41375-025-02667-7"}], "notes": [], "created": "2026-09-23T13:18:58.441Z", "modified": "2026-09-23T13:18:59.106Z"}, {"entity": "publication", "iuid": "a9f63d89f6d145709b1dbad0563f9599", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a9f63d89f6d145709b1dbad0563f9599.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a9f63d89f6d145709b1dbad0563f9599"}}, "title": "The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia.", "authors": [{"family": "H\u00e4gerstrand", "given": "Daniel", "initials": "D", "orcid": "0000-0001-7270-0776", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c3221dc6f79b4d77bea303ab5e2b6fd2.json"}}, {"family": "Oder", "given": "Bla\u017e", "initials": "B", "orcid": "0000-0001-7984-3104", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6acdc03dd23b48f69513caffa29dba4c.json"}}, {"family": "Cortese", "given": "Diego", "initials": "D"}, {"family": "Qu", "given": "Ying", "initials": "Y"}, {"family": "Binzer-Panchal", "given": "Amrei", "initials": "A", "orcid": "0000-0002-0472-0609", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/101ef607727744cda1a83ed436b81bbf.json"}}, {"family": "\u00d6sterholm", "given": "Cecilia", "initials": "C"}, {"family": "Del Peso Santos", "given": "Teresa", "initials": "T"}, {"family": "Rabbani", "given": "Leily", "initials": "L"}, {"family": "Asl", "given": "Hassan Foroughi", "initials": "HF"}, {"family": "Skaftason", "given": "Aron", "initials": "A"}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Lundholm", "given": "August", "initials": "A"}, {"family": "Koutroumani", "given": "Maria", "initials": "M"}, {"family": "Haider", "given": "Zahra", "initials": "Z"}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "Mollstedt", "given": "John", "initials": "J"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Plevova", "given": "Karla", "initials": "K"}, {"family": "Agathangelidis", "given": "Andreas", "initials": "A", "orcid": "0000-0002-8467-7945", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ad1d5ceba7c74c52ba492aaaa195f9cf.json"}}, {"family": "Scarf\u00f2", "given": "Lydia", "initials": "L", "orcid": "0000-0002-0844-0989", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7697d7b279ae48a387843c617f30fa3c.json"}}, {"family": "Armand", "given": "Marine", "initials": "M", "orcid": "0000-0001-8906-3128", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4076e069779745059ba33556a6f4b295.json"}}, {"family": "Muggen", "given": "Alice F", "initials": "AF"}, {"family": "Kay", "given": "Neil E", "initials": "NE", "orcid": "0000-0002-5951-5055", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8ed8e38f552b44c28e3a32023c07b537.json"}}, {"family": "Shanafelt", "given": "Tait", "initials": "T"}, {"family": "Rossi", "given": "Davide", "initials": "D"}, {"family": "Orre", "given": "Lukas M", "initials": "LM", "orcid": "0000-0002-0384-1003", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e290f7cb5dfd49eb93e63cb704459516.json"}}, {"family": "Pospisilova", "given": "Sarka", "initials": "S", "orcid": "0000-0001-7136-2680", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/75467f2097fe4bcfb274e40e46cfbf12.json"}}, {"family": "Barylyuk", "given": "Konstantin", "initials": "K", "orcid": "0000-0002-3580-0345", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d7bedc9259c24ef18384873aaf5da3f0.json"}}, {"family": "Davi", "given": "Frederic", "initials": "F"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e443cdb01cc44a7fa786941b5c0b62d6.json"}}, {"family": "Langerak", "given": "Anton W", "initials": "AW", "orcid": "0000-0002-2078-3220", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/535a658cf9db4176b46671be08e4f909.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/561efcf32e2648c8a10fee692fc4e908.json"}}, {"family": "Ghia", "given": "Paolo", "initials": "P", "orcid": "0000-0003-3750-7342", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/475d35f1a3c446819b2f24be819c2dee.json"}}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K", "orcid": "0000-0001-8529-640X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f6107d6f774ee6acb2c66ecfcb90cc.json"}}, {"family": "Sutton", "given": "Lesley-Ann", "initials": "LA"}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc038c13a8cb44bd93f3552ed250a179.json"}}], "type": "journal article", "published": "2024-11-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "38", "issue": "11", "pages": "2429-2442", "issn-l": "0887-6924"}, "abstract": "SF3B1 mutations are recurrent in chronic lymphocytic leukemia (CLL), particularly enriched in clinically aggressive stereotyped subset #2. To investigate their impact, we conducted RNA-sequencing of 18 SF3B1MUT and 17 SF3B1WT subset #2 cases and identified 80 significant alternative splicing events (ASEs). Notable ASEs concerned exon inclusion in the non-canonical BAF (ncBAF) chromatin remodeling complex subunit, BRD9, and splice variants in eight additional ncBAF complex interactors. Long-read RNA-sequencing confirmed the presence of splice variants, and extended analysis of 139 CLL cases corroborated their association with SF3B1 mutations. Overexpression of SF3B1K700E induced exon inclusion in BRD9, resulting in a novel splice isoform with an alternative C-terminus. Protein interactome analysis of the BRD9 splice isoform revealed augmented ncBAF complex interaction, while exhibiting decreased binding of auxiliary proteins, including SPEN, BRCA2, and CHD9. Additionally, integrative multi-omics analysis identified a ncBAF complex-bound gene quartet on chromosome 1 with higher expression levels and more accessible chromatin in SF3B1MUT CLL. Finally, Cancer Dependency Map analysis and BRD9 inhibition displayed BRD9 dependency and sensitivity in cell lines and primary CLL cells. In conclusion, spliceosome dysregulation caused by SF3B1 mutations leads to multiple ASEs and an altered ncBAF complex interactome, highlighting a novel pathobiological mechanism in SF3B1MUT CLL.", "doi": "10.1038/s41375-024-02379-4", "pmid": "39261602", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11518989"}, {"db": "pii", "key": "10.1038/s41375-024-02379-4"}, {"db": "figshare", "key": "10.17044/scilifelab.21694799"}], "notes": [], "created": "2026-09-23T12:27:07.552Z", "modified": "2026-09-23T12:27:07.939Z"}]}