Abstract
BackgroundMutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting.MethodsWe examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2).ResultsThe mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083).ConclusionOur findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1493-5) contains supplementary material, which is available to authorized users.
Highlights
Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated
Among the 129 MDS patients, nine were identified as harboring a mutation in Splicing factor 3 subunit b1 (SF3B1) (7.0 %), 10 patients had mutations in U2 small nuclear RNA auxiliary factor 1 (U2AF1) (7.8 %), and 13 patients exhibited a mutation in serine arginine-rich splicing factor 2 (SRSF2) (10.1 %)
Our findings indicate that the SF3B1, U2AF1, and SRSF2 mutations were relatively infrequent in MDS patients without RS, contradicting the results from a previous study
Summary
Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. A number of gene mutations and cytogenetic changes have been implicated in the pathogenesis of MDS, including mutations in RAS, TP53, and RUNX1. Mutations in these genes do not fully explain the pathogenesis of MDS as these mutations are commonly found in other myeloid malignancies. The genetic alterations responsible for dysplastic phenotypes and ineffective hematopoiesis of myelodysplasia are poorly understood [3]
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