Back to Search
Start Over
Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia
- Source :
- Oncotarget
- Publication Year :
- 2015
-
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 :
- 0301 basic medicine
Oncology
Male
medicine.disease_cause
Bioinformatics
chemistry.chemical_compound
0302 clinical medicine
hemic and lymphatic diseases
Sanger sequencing
Aged, 80 and over
de novo AML
Mutation
Serine-Arginine Splicing Factors
Myeloid leukemia
Middle Aged
Isocitrate Dehydrogenase
DNA-Binding Proteins
Leukemia, Myeloid, Acute
RUNX1
030220 oncology & carcinogenesis
Core Binding Factor Alpha 2 Subunit
symbols
splicing factor mutations
Female
RNA Splicing Factors
Research Paper
Adult
medicine.medical_specialty
RNA Splicing
IDH2
Disease-Free Survival
Dioxygenases
03 medical and health sciences
Splicing factor
symbols.namesake
Young Adult
Internal medicine
Proto-Oncogene Proteins
medicine
Humans
Clinical significance
neoplasms
Aged
Base Sequence
business.industry
Cytogenetics
Sequence Analysis, DNA
Phosphoproteins
Splicing Factor U2AF
paired sample
Repressor Proteins
030104 developmental biology
chemistry
prognosis
business
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....bb4c90f25d78eb532b13765fc41a23f3