臺大醫院-內科部;臺大醫院-病理部;臺大醫院-檢驗醫學部;臺大醫學院;臺大醫學院-腫瘤醫學研究所;HSIN-AN HOULiu, Chieh-YuChieh-YuLiuKuo, Yuan-YehYuan-YehKuoWEN-CHIEN CHOUCHENG-HONG TSAICHIEN-CHIN LINLIANG-IN LINTseng, Mei-HsuanMei-HsuanTsengChiang, Ying-ChiehYing-ChiehChiangLiu, Ming-ChihMing-ChihLiuLiu, Chia-WenChia-WenLiuJIH-LUH TANGMING YAOLi, Chi-ChengChi-ChengLiSHANG-YI HUANGBOR-SHENG KOSZU-CHUN HSUChen, Chien-YuanChien-YuanChenLin, Chien-TingChien-TingLinSHANG-JU WUWOEI TSAYHWEI-FANG TIEN2017-04-252018-07-112017-04-252018-07-1120161949-2553http://ntur.lib.ntu.edu.tw//handle/246246/278739https://www.scopus.com/record/display.uri?eid=2-s2.0-84961589389&doi=10.18632%2foncotarget.7000&origin=inward&txGid=21b80847bb0069e3ce8014408892882eMutations in splicing factor (SF) genes are frequently detected in myelodysplastic syndrome, but the prognostic relevance of these genes mutations in acute myeloid leukemia (AML) remains unclear. In this study, we investigated mutations of three SF genes, SF3B1, U2AF1 and SRSF2, by Sanger sequencing in 500 patients with de novo AML and analysed their clinical relevance. SF mutations were identified in 10.8% of total cohort and 13.2% of those with intermediate-risk cytogenetics. SF mutations were closely associated with RUNX1, ASXL1, IDH2 and TET2 mutations. SF-mutated AML patients had a significantly lower complete remission rate and shorter disease-free survival (DFS) and overall survival (OS) than those without the mutation. Multivariate analysis demonstrated that SF mutation was an independent poor prognostic factor for DFS and OS. A scoring system incorporating SF mutation and ten other prognostic factors was proved very useful to risk-stratify AML patients. Sequential study of paired samples showed that SF mutations were stable during AML evolution. In conclusion, SF mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression. These mutations may be potential targets for novel treatment and biomarkers for disease monitoring in AML.de novo AMLsplicing factor mutationsprognosispaired samplejournal article10.18632/oncotarget.700026812887