SRSF2 mutations in primary myelofibrosis: Significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival

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

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Abstract

Among spliceosome component mutations, those involving SF3B1 are most frequent in myelodysplastic syndromes with ring sideroblasts (MDS-RS; ∼75% incidence) and SRSF2 in chronic myelomonocytic leukemia (∼28% incidence). We recently reported on the lack of prognostic significance for SF3B1 mutations in both MDS-RS and primary myelofibrosis (PMF). In the current study, we examined the prevalence and prognostic relevance of SRSF2 mutations in PMF. Among 187 patients screened, 32 (17%) harbored SRSF2 monoallelic mutations affecting residue P95. Significant associations were demonstrated between SRSF2 mutations and advanced age (P < .01), IDH mutations (P < .01), and higher DIPSS-plus risk category (P = .03). SRSF2 mutations 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 IDH mutations (P < .01; HR = 2.3; 95% CI, 1.4-3.8). In conclusion, SRSF2 mutations are relatively common in PMF, cluster with IDH mutations, and are independently predictive of poor outcome.

Original languageEnglish (US)
Pages (from-to)4168-4171
Number of pages4
JournalBlood
Volume120
Issue number20
DOIs
StatePublished - Nov 15 2012

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Primary Myelofibrosis
Cluster Analysis
Leukemia
Mutation
Survival
Leukemia, Myelomonocytic, Chronic
Spliceosomes
Myelodysplastic Syndromes
Incidence

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

SRSF2 mutations in primary myelofibrosis : Significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival. / Lasho, Terra L.; Jimma, Thitina; Finke, Christy M.; Patnaik, Mrinal M; Hanson, Curtis A.; Ketterling, Rhett P.; Pardanani, Animesh D; Tefferi, Ayalew.

In: Blood, Vol. 120, No. 20, 15.11.2012, p. 4168-4171.

Research output: Contribution to journalArticle

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abstract = "Among spliceosome component mutations, those involving SF3B1 are most frequent in myelodysplastic syndromes with ring sideroblasts (MDS-RS; ∼75{\%} incidence) and SRSF2 in chronic myelomonocytic leukemia (∼28{\%} incidence). We recently reported on the lack of prognostic significance for SF3B1 mutations in both MDS-RS and primary myelofibrosis (PMF). In the current study, we examined the prevalence and prognostic relevance of SRSF2 mutations in PMF. Among 187 patients screened, 32 (17{\%}) harbored SRSF2 monoallelic mutations affecting residue P95. Significant associations were demonstrated between SRSF2 mutations and advanced age (P < .01), IDH mutations (P < .01), and higher DIPSS-plus risk category (P = .03). SRSF2 mutations 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 IDH mutations (P < .01; HR = 2.3; 95{\%} CI, 1.4-3.8). In conclusion, SRSF2 mutations are relatively common in PMF, cluster with IDH mutations, and are independently predictive of poor outcome.",
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T2 - Significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival

AU - Lasho, Terra L.

AU - Jimma, Thitina

AU - Finke, Christy M.

AU - Patnaik, Mrinal M

AU - Hanson, Curtis A.

AU - Ketterling, Rhett P.

AU - Pardanani, Animesh D

AU - Tefferi, Ayalew

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N2 - Among spliceosome component mutations, those involving SF3B1 are most frequent in myelodysplastic syndromes with ring sideroblasts (MDS-RS; ∼75% incidence) and SRSF2 in chronic myelomonocytic leukemia (∼28% incidence). We recently reported on the lack of prognostic significance for SF3B1 mutations in both MDS-RS and primary myelofibrosis (PMF). In the current study, we examined the prevalence and prognostic relevance of SRSF2 mutations in PMF. Among 187 patients screened, 32 (17%) harbored SRSF2 monoallelic mutations affecting residue P95. Significant associations were demonstrated between SRSF2 mutations and advanced age (P < .01), IDH mutations (P < .01), and higher DIPSS-plus risk category (P = .03). SRSF2 mutations 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 IDH mutations (P < .01; HR = 2.3; 95% CI, 1.4-3.8). In conclusion, SRSF2 mutations are relatively common in PMF, cluster with IDH mutations, and are independently predictive of poor outcome.

AB - Among spliceosome component mutations, those involving SF3B1 are most frequent in myelodysplastic syndromes with ring sideroblasts (MDS-RS; ∼75% incidence) and SRSF2 in chronic myelomonocytic leukemia (∼28% incidence). We recently reported on the lack of prognostic significance for SF3B1 mutations in both MDS-RS and primary myelofibrosis (PMF). In the current study, we examined the prevalence and prognostic relevance of SRSF2 mutations in PMF. Among 187 patients screened, 32 (17%) harbored SRSF2 monoallelic mutations affecting residue P95. Significant associations were demonstrated between SRSF2 mutations and advanced age (P < .01), IDH mutations (P < .01), and higher DIPSS-plus risk category (P = .03). SRSF2 mutations 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 IDH mutations (P < .01; HR = 2.3; 95% CI, 1.4-3.8). In conclusion, SRSF2 mutations are relatively common in PMF, cluster with IDH mutations, and are independently predictive of poor outcome.

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