Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms
Menée sur 533 patients atteints d'un syndrome myélodysplasique, d'une maladie myéloproliférative ou d'une leucémie myéloïde aiguë ayant évolué à partir d'un syndrome myélodysplasique, cette étude analyse l'association entre des mutations du gène SF3B1 et divers paramètres cliniques
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 150/533 (28.1%) patients with MDS, 16/83 (19.3%) with MDS/MPN, and 2/38 (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% CI, 93.5-99.5%). In multivariate analysis including established risk factors, SF3B1 mutations were found to be independently associated with better overall survival (HR=0.15, P=.025) and lower risk of evolution into AML (HR=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