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  4. Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia
 
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Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia

Resource
Oncotarget, 7(8), 9084-9101
Journal
Oncotarget
Journal Volume
7
Journal Issue
8
Pages
9084
Date Issued
2016
Date
2016
Author(s)
HSIN-AN HOU  
Liu, Chieh-Yu
Kuo, Yuan-Yeh
WEN-CHIEN CHOU  
CHENG-HONG TSAI  
CHIEN-CHIN LIN  
LIANG-IN LIN  
Tseng, Mei-Hsuan
Chiang, Ying-Chieh
Liu, Ming-Chih
Liu, Chia-Wen
JIH-LUH TANG  
MING YAO  
Li, Chi-Cheng
SHANG-YI HUANG  
BOR-SHENG KO  
SZU-CHUN HSU  
Chen, Chien-Yuan  
Lin, Chien-Ting
SHANG-JU WU  
WOEI TSAY  
HWEI-FANG TIEN  
DOI
10.18632/oncotarget.7000
URI
http://ntur.lib.ntu.edu.tw//handle/246246/278739
https://www.scopus.com/record/display.uri?eid=2-s2.0-84961589389&doi=10.18632%2foncotarget.7000&origin=inward&txGid=21b80847bb0069e3ce8014408892882e
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 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.
Subjects
de novo AML
splicing factor mutations
prognosis
paired sample
Publisher
Impact Journals LLC
Type
journal article

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