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11. SRSF2mutations in primary myelofibrosis: significant clustering with IDHmutations and independent association with inferior overall and leukemia-free survival

Author

Lasho, Terra L., Jimma, Thitina, Finke, Christy M., Patnaik, Mrinal, Hanson, Curtis A., Ketterling, Rhett P., Pardanani, Animesh, and Tefferi, Ayalew

Abstract

Among spliceosome component mutations, those involving SF3B1are most frequent in myelodysplastic syndromes with ring sideroblasts (MDS-RS; ∼ 75% incidence) and SRSF2in chronic myelomonocytic leukemia (∼ 28% incidence). We recently reported on the lack of prognostic significance for SF3B1mutations in both MDS-RS and primary myelofibrosis (PMF). In the current study, we examined the prevalence and prognostic relevance of SRSF2mutations in PMF. Among 187 patients screened, 32 (17%) harbored SRSF2monoallelic mutations affecting residue P95. Significant associations were demonstrated between SRSF2mutations and advanced age (P< .01), IDHmutations (P< .01), and higher DIPSS-plus risk category (P= .03). SRSF2mutations were associated with shortened overall (P< .01) and leukemia-free (P< .01) survival; the adverse effect on survival was independent of DIPSS-plus (P= .01; HR = 1.9; 95% CI, 1.1-3.0) and IDHmutations (P< .01; HR = 2.3; 95% CI, 1.4-3.8). In conclusion, SRSF2mutations are relatively common in PMF, cluster with IDHmutations, and are independently predictive of poor outcome.

Published
2012
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