{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T01:29:15Z","timestamp":1770686955821,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>SF3B1-mutated myelodysplastic syndrome (MDS) is a distinct entity associated with a favorable prognosis. Recent data suggest that certain SF3B1 variants portend a worse prognosis. Our study aims to (1) describe SF3B1-MDS patients from a single tertiary center in Singapore and (2) determine if variant type holds prognostic value. We identified MDS patients with SF3B1 variants via next-generation sequencing (NGS) performed from 1 November 2021 to 31 October 2025 at Singapore General Hospital. Extracted genomic material from marrow or blood samples was amplified. Libraries were prepared, sequenced, and analyzed, and the hematological parameters, mutation profiles, and outcomes were evaluated. Twenty-five patients had SF3B1-MDS. Ten SF3B1 variants were found, and the three most prevalent were K700E (42%), K666N (19%), and R625C (7.7%). The median variant allele frequency (VAF) was 30% (IQR: 11\u201336%). Twelve patients (48%) had \u22651 co-mutations. Variant type and VAF had no impact on disease progression; only the presence of \u22651 co-mutations increased the progression chances. In our study, the analysis of SF3B1 variant type was inconclusive and showed no demonstrable statistical association with disease progression. However, the number of co-mutations affected the prognosis of patients. As SF3B1-MDS is heterogenous, further studies are needed to capture its diversity and identify features required to improve risk stratification and personalized treatment.<\/jats:p>","DOI":"10.3390\/ijms27031423","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:38:34Z","timestamp":1769794714000},"page":"1423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Characteristics and Molecular Profiling of SF3B1-Mutated Myelodysplastic Syndrome (MDS) in a Real-World Practice"],"prefix":"10.3390","volume":"27","author":[{"given":"Ruonan Roni","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore"},{"name":"Department of Haematology, National University Hospital, Singapore 119074, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-083X","authenticated-orcid":false,"given":"Hein","family":"Than","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Tham","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gee Fung","family":"How","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si Jie","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tertius T.","family":"Tuy","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.1182\/bloodadvances.2023011260","article-title":"The E592K variant of SF3B1 creates unique RNA missplicing and associates with high-risk MDS without ring sideroblasts","volume":"8","author":"Choi","year":"2024","journal-title":"Blood Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1182\/bloodadvances.2019001127","article-title":"The K666N mutation in SF3B1 is associated with increased progression of MDS and distinct RNA splicing","volume":"4","author":"Dalton","year":"2020","journal-title":"Blood Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1182\/blood-2012-03-420489","article-title":"Revised international prognostic scoring system for myelodysplastic syndromes","volume":"120","author":"Greenberg","year":"2012","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1038\/s41375-022-01613-1","article-title":"The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic\/Dendritic Neoplasms","volume":"36","author":"Khoury","year":"2022","journal-title":"Leukemia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1261\/rna.080368.124","article-title":"SF3B1: From core splicing factor to oncogenic driver","volume":"31","author":"Manley","year":"2025","journal-title":"RNA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"24","DOI":"10.46989\/001c.142956","article-title":"Beyond Hypomethylating Agents: Novel Therapies and Targeted Approaches","volume":"7","author":"Cortiana","year":"2025","journal-title":"Clin. Hematol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1182\/blood-2013-08-518886","article-title":"Clinical and biological implications of driver mutations in myelodysplastic syndromes","volume":"122","author":"Papaemmanuil","year":"2013","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1136\/jclinpath-2019-205895","article-title":"Somatic SF3B1 mutations in myelodysplastic syndrome with ring sideroblasts and chronic lymphocytic leukaemia","volume":"72","author":"Foy","year":"2019","journal-title":"J. Clin. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1038\/s41375-022-01728-5","article-title":"SF3B1 mutated MDS: Blast count, genetic co-abnormalities and their impact on classification and prognosis","volume":"36","author":"Huber","year":"2022","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1182\/blood.2020004850","article-title":"SF3B1-mutant MDS as a distinct disease subtype: A proposal from the International Working Group for the Prognosis of MDS","volume":"136","author":"Malcovati","year":"2020","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"985","DOI":"10.21873\/invivo.13172","article-title":"Co-mutation of ASXL1 and SF3B1 Predicts Poorer Overall Survival Than Isolated ASXL1 or SF3B1 Mutations","volume":"37","author":"Song","year":"2023","journal-title":"In Vivo"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.21873\/cgp.20115","article-title":"Does SF3B1\/TET2 Double Mutation Portend Better or Worse Prognosis Than Isolated SF3B1 or TET2 Mutation?","volume":"16","author":"Song","year":"2019","journal-title":"Cancer Genom. Proteom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1182\/blood-2014-11-610543","article-title":"Acute myeloid leukemia ontogeny is defined by distinct somatic mutations","volume":"125","author":"Lindsley","year":"2015","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3343\/alm.2024.0079","article-title":"Reclassification of Myelodysplastic Neoplasms According to the 2022 World Health Organization Classification and the 2022 International Consensus Classification Using Open-Source Data: Focus on SF3B1- and TP53-mutated Myelodysplastic Neoplasms","volume":"45","author":"Yun","year":"2025","journal-title":"Ann. Lab. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/ajcp\/aqaa016","article-title":"Comparison of SF3B1\/DNMT3A Comutations With DNMT3A or SF3B1 Mutation Alone in Myelodysplastic Syndrome and Clonal Cytopenia of Undetermined Significance","volume":"154","author":"Song","year":"2020","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1182\/blood-2011-09-377275","article-title":"Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic\/myeloproliferative neoplasms","volume":"118","author":"Malcovati","year":"2011","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e70930","DOI":"10.1002\/cam4.70930","article-title":"Significance of Mutation Spots and Concurrent Gene Mutations on Prognosis and Clinical Outcomes in Myelodysplastic Syndromes with SF3B1 Mutation","volume":"14","author":"Liu","year":"2025","journal-title":"Cancer Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e70017","DOI":"10.1002\/cncr.70017","article-title":"Splicing factor 3b subunit 1 mutation patterns and prognostic implications in myelodysplastic syndromes, acute myeloid leukemia, and chronic lymphocytic leukemia: A retrospective study of 1691 cases","volume":"131","author":"Qiao","year":"2025","journal-title":"Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1002\/cncr.33745","article-title":"Only SF3B1 mutation involving K700E independently predicts overall survival in myelodysplastic syndromes","volume":"127","author":"Sasaki","year":"2021","journal-title":"Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e13393b9","DOI":"10.1097\/01.HS9.0000969664.13393.b9","article-title":"P690: Identification of clinically relevant variant-level sex-bias in SF3B1 K700\/K666 and IDH2 R140\/R172","volume":"7","author":"Sakuma","year":"2023","journal-title":"HemaSphere"},{"key":"ref_21","first-page":"4476","article-title":"Impact of mutational variant allele frequency on prognosis in myelodysplastic syndromes","volume":"10","author":"Jiang","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1158\/2643-3230.BCD-25-0047","article-title":"Multimodal and Data-Driven Assessment of Myeloid Neoplasms Refines Classification across Disease States","volume":"6","author":"Lachowiez","year":"2025","journal-title":"Blood Cancer Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/ajh.25267","article-title":"Mutations and karyotype predict treatment response in myelodysplastic syndromes","volume":"93","author":"Idossa","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2506858","DOI":"10.1080\/16078454.2025.2506858","article-title":"Luspatercept for the treatment of lower-risk myelodysplastic syndrome with SF3B1 mutation: A real-world single-center research in China","volume":"30","author":"Liang","year":"2025","journal-title":"Hematology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1056\/NEJMoa1908892","article-title":"Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes","volume":"382","author":"Fenaux","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e70086","DOI":"10.1002\/hem3.70086","article-title":"Response to luspatercept can be predicted and improves overall survival in the real-life treatment of LR-MDS","volume":"9","author":"Consagra","year":"2025","journal-title":"HemaSphere"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1423\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:16:26Z","timestamp":1770624986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031423"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031423","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]}}}