TY - JOUR
T1 - SRSF2 mutations in primary myelofibrosis
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
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Pardanani, Animesh
AU - Tefferi, Ayalew
PY - 2012/11/15
Y1 - 2012/11/15
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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U2 - 10.1182/blood-2012-05-429696
DO - 10.1182/blood-2012-05-429696
M3 - Article
C2 - 22968464
AN - SCOPUS:84869786872
SN - 0006-4971
VL - 120
SP - 4168
EP - 4171
JO - Blood
JF - Blood
IS - 20
ER -