Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression
Journal
American Journal of Hematology
Journal Volume
88
Journal Issue
11
Pages
E277-E282
Date Issued
2013
Author(s)
Lin C.-T.
Kuo Y.-Y.
Li L.-Y.
Tseng M.-H.
Huang C.-F.
Lai Y.-J.
Lee F.-Y.
Liu M.-C.
Liu C.-W.
Abstract
We aimed to analyze clinical impacts of the U2AF1 mutation on patients with myelodysplastic syndrome (MDS) and its stability during disease progression. We checked mutation status of the U2AF1 by direct sequencing in 478 de novo MDS patients and correlated with the clinical characteristics and outcomes. We also sequentially analyzed the U2AF1 mutation in 421 samples from 142 patients to determine its stability during the disease courses. Thirty-six patients (7.5%) were found to have U2AF1 mutations, which occurred more frequently in younger patients (P=0.033). U2AF1 mutation was an independent poor-risk factor for overall survival (OS) in all patients (P=0.030) and younger patients (P=0.041). U2AF1 mutation could also predict shorter time-to-leukemia transformation (TTL) in younger patients (P=0.020). In addition, U2AF1 mutation was associated with shorter TTL in lower-risk MDS patients. Sequential analyses showed all original U2AF1 mutations in U2AF1-mutated patients were retained during follow-ups unless complete remission was achieved, whereas none of the U2AF1-wild patients acquired a novel mutation during disease evolution. U2AF1 mutation is more prevalent in younger MDS patients and associated with inferior outcomes although it is stable during the clinical course. The mutation may be used as a biomarker for risk stratification. Am. J. Heamtol. 88:E277-E282, 2013. ? 2013 Wiley Periodicals, Inc. ? 2013 Wiley Periodicals, Inc.
SDGs
Other Subjects
antineoplastic agent; DNA methyltransferase 3A; Janus kinase 2; transcription factor RUNX1; adolescent; adult; aged; allogeneic hematopoietic stem cell transplantation; article; cancer chemotherapy; chronic myelomonocytic leukemia; clinical feature; correlational study; disease course; exon; female; follow up; gene; gene mutation; gene sequence; genetic association; genetic stability; genetic transformation; groups by age; human; human cell; leukemia remission; major clinical study; male; mononuclear cell; mutation rate; mutational analysis; myelodysplastic syndrome; oncological parameters; overall survival; priority journal; prognosis; refractory cytopenia with multilineage dysplasia; refractory cytopenia with multilineage dysplasia and ringed sideroblasts; risk assessment; risk factor; time to leukemia transformation; u2af1 gene; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Cell Transformation, Neoplastic; Cohort Studies; Disease Progression; DNA Mutational Analysis; Female; Follow-Up Studies; Genetic Association Studies; Humans; Leukemia; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Nuclear Proteins; Prognosis; Ribonucleoproteins; Survival Analysis; Taiwan; Young Adult
Type
journal article