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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.

Original publication

DOI

10.1182/blood-2011-09-377275

Type

Journal article

Journal

Blood

Publication Date

08/12/2011

Volume

118

Pages

6239 - 6246

Keywords

Aged, Alleles, Codon, DNA Mutational Analysis, Erythroblasts, Female, Follow-Up Studies, Genetic Association Studies, Humans, Leukemia, Myeloid, Acute, Male, Middle Aged, Mutation, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Phosphoproteins, Prognosis, RNA Splicing Factors, Ribonucleoprotein, U2 Small Nuclear, Sex Characteristics, Survival Analysis