期刊
BLOOD
卷 118, 期 24, 页码 6239-6246出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-09-377275
关键词
-
类别
资金
- Associazione Italiana per la Ricerca sul Cancro [1005]
- Fondazione Cariplo
- Regione Lombardia
- Italian Ministry of Health
- Wellcome Trust [077012/Z/05/Z, WT088340MA]
- Kay Kendall Leukaemia Fund
- Tayside Tissue Bank
- Tayside Leukemia Research and Endowment Fund
- Medical Research Council
- Leukaemia Lymphoma Research
- Oxford National Institute for Health Research Biomedical Research Center
- Swedish Cancer Society
- Scientific Research Council
- Cancer Society in Stockholm
In a previous study, we identified somatic mutations of SF3B1, a gene encoding a core component of RNA splicing machinery, in patients with myelodysplastic syndrome (MDS). Here, we define the clinical significance of these mutations in MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). The coding exons of SF3B1 were screened using massively parallel pyrosequencing in patients with MDS, MDS/MPN, or acute myeloid leukemia (AML) evolving from MDS. Somatic mutations of SF3B1 were found in 150 of 533 (28.1%) patients with MDS, 16 of 83 (19.3%) with MDS/MPN, and 2 of 38 (5.3%) with AML. There was a significant association of SF3B1 mutations with the presence of ring sideroblasts (P < .001) and of mutant allele burden with their proportion (P = .002). The mutant gene had a positive predictive value for ring sideroblasts of 97.7% (95% confidence interval, 93.5%-99.5%). In multivariate analysis including established risk factors, SF3B1 mutations were found to be independently associated with better overall survival (hazard ratio = 0.15, P = .025) and lower risk of evolution into AML (hazard ratio = 0.33, P = .049). The close association between SF3B1 mutations and disease phenotype with ring sideroblasts across MDS and MDS/MPN is consistent with a causal relationship. Furthermore, SF3B1 mutations are independent predictors of favorable clinical outcome, and their incorporation into stratification systems might improve risk assessment in MDS. (Blood. 2011;118(24):6239-6246)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据