{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:46:47Z","timestamp":1791996407135,"version":"4.4.0"},"reference-count":30,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"abstract":"Introduction: The clinical and prognostic significance of splicing factor (SF) mutations in newly diagnosed adult de novo acute myeloid leukemia (AML) remains incompletely defined. This study aimed to characterize the clinical features, co-mutation profiles, treatment responses, and prognostic impact of SF mutations in this population. Methods: We retrospectively analyzed 323 newly diagnosed adult patients with de novo non-acute promyelocytic leukemia AML treated between 2015 and 2023. Targeted next-generation sequencing assessed at least 32 recurrently mutated genes. SF-mutated (SFmut) status was defined by the presence of mutations in SF3B1, SRSF2, U2AF1, or ZRSR2. Clinical characteristics, co-mutation profiles, treatment regimens, treatment responses, and survival outcomes were compared between the SFmut and SF-wild-type (SFwt) groups. Survival was analyzed using Kaplan-Meier methods and Cox proportional hazards models. Results: SF mutations were identified in 58 of 323 patients (17.96%) and were largely mutually exclusive. Compared with SFwt patients, SFmut patients were more often male and older, had a higher CD4\/CD8 ratio, and more frequently received low-intensity therapy. SFmut cases were enriched for co-mutations in ASXL1, RUNX1, CBL, IDH1, PHF6, SETBP1, BCORL1, and STAG2. The SFmut group had a lower composite complete remission rate than the SFwt group (50.9% vs. 71.3%, <inline-formula><mml:math id=\"m1\" xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mrow><mml:mi>p<\/mml:mi><mml:mo>=<\/mml:mo><mml:mn>0.003<\/mml:mn><\/mml:mrow><\/mml:math><\/inline-formula>) and significantly shorter overall survival (median, 6.73 vs. 19.07 months; <inline-formula><mml:math id=\"m2\" xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mml:mrow><mml:mi>p<\/mml:mi><mml:mspace width=\"0.25em\" \/><mml:mo><<\/mml:mo><mml:mspace width=\"0.25em\" \/><mml:mn>0.001<\/mml:mn><\/mml:mrow><\/mml:math><\/inline-formula>). In the overall multivariable model, SFmut status, age \u226565 years, and WBC \u2265100 \u00d7 109\/L were independently associated with inferior overall survival, whereas intensive therapy was independently protective. Intermediate and adverse cytogenetic risk were also associated with progressively worse overall survival. SFmut status showed nonsignificant trends toward shorter overall survival in both treatment strata and was independently associated with poorer overall survival in the non-intensive, but not the intensive, subgroup; however, the interaction between SF status and treatment intensity was not significant. Exploratory unadjusted co-mutation analyses showed the most consistent adverse signals for SF\/ASXL1 and SF\/RUNX1, whereas other findings were heterogeneous or based on small subgroups. Conclusion: SF mutations define a clinically distinct subgroup of newly diagnosed adult de novo AML characterized by adverse co-mutation profiles, lower remission rates, and inferior survival. Their adverse prognostic effect was most evident among patients receiving non-intensive therapy, although no significant interaction with treatment intensity was observed. The prognostic implications of individual SF co-mutation patterns require validation in larger independent cohorts.<\/jats:p>","DOI":"10.1159\/aha\/abkag006","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:17:42Z","timestamp":1790335062000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Features and Prognostic Impact of Splicing Factor Mutations and Their Co-Mutations in Acute Myeloid Leukemia"],"prefix":"10.1159","author":[{"given":"Beibei","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanying","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furun","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianshan","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10496"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103283"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-373159"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015850"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100728"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00384-z"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.51"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4165"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004556"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006868"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-023-00922-7"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-024-02374-9"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020004850"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2200008"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022016867"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-139470"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.06.032"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-687830"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74744-z"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04462-8"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0610"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2020.252825"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020004173"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0103-x"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.038"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1177\/20406207251347344"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12047"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.906355"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.047"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado4274"}],"container-title":["Acta 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