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Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia.
- Source :
-
Oncotarget [Oncotarget] 2016 Feb 23; Vol. 7 (8), pp. 9084-101. - Publication Year :
- 2016
-
Abstract
- Mutations 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 SFmutation 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Base Sequence
Core Binding Factor Alpha 2 Subunit genetics
DNA-Binding Proteins genetics
Dioxygenases
Disease-Free Survival
Female
Humans
Isocitrate Dehydrogenase genetics
Male
Middle Aged
Mutation genetics
Proto-Oncogene Proteins genetics
Repressor Proteins genetics
Sequence Analysis, DNA
Young Adult
Leukemia, Myeloid, Acute genetics
Phosphoproteins genetics
RNA Splicing genetics
RNA Splicing Factors genetics
Serine-Arginine Splicing Factors genetics
Splicing Factor U2AF genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26812887
- Full Text :
- https://doi.org/10.18632/oncotarget.7000