Impact of splicing factor mutations on clinical features in patients with myelodysplastic syndromes
Impact of splicing factor mutations on clinical features in patients with myelodysplastic syndromes
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DOI：
10.1007/s12185-018-2551-y
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发表时间：
2018-12-01
影响因子：
2.1
通讯作者：
Harada, Hironori
中科院分区：
文献类型：
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作者：
Shingai, Naoki;Harada, Yuka;Harada, Hironori
剪接因子基因突变在60-70%的骨髓增生异常综合征(MDS)患者中被发现。我们研究了剪接因子基因突变对MDS的诊断、患者特征和预后的影响。共纳入106例MDS患者。2017年世界卫生组织分类中有环状铁粒母细胞的MDS患者的比例(14.15%)显著高于2008年世界卫生组织分类中的环状铁粒母细胞难治性贫血患者(2.88%)(P=0.005)。在32例患者中检测到剪接因子突变(13例SF3B1，8例U2AF1，11例SRSF2)，这些突变是互斥的。不同突变的患者在平均红细胞体积、血小板计数、骨髓髓系/红系比率、巨核细胞计数等方面存在显著差异。SRSF2突变与红细胞输注依赖的累积发生率高相关，而SF3B1突变与浓缩血小板输注依赖的累积发生率低相关。SF3B1突变的存在是总体生存的显著单变量预测因子，但在多变量模型中变得不显著。虽然许多因素也可能影响生存率，但这些结果表明，剪接因子突变有助于不同的MDS表型，包括患者特征和临床病程。
Splicing factor gene mutations are found in 60-70% of patients with myelodysplastic syndromes (MDS). We investigated the effects of splicing factor gene mutations on the diagnosis, patient characteristics, and prognosis of MDS. A total of 106 patients with MDS were included. The percentage of patients with MDS with ring sideroblasts (14.15%) as per the 2017 WHO classification was significantly higher than that of patients with refractory anemia with ring sideroblasts (2.88%) as per the 2008 WHO classification (P=0.005). Splicing factor mutations were detected in 32 patients (13 SF3B1, 8 U2AF1, and 11 SRSF2), and the mutations were mutually exclusive. Significant differences were observed in the mean corpuscular volume, platelet count, bone marrow myeloid:erythroid ratio, and megakaryocyte count in patients with different mutations. SRSF2 mutations were associated with a high cumulative incidence of red blood cell transfusion dependence, while SF3B1 mutations were associated with a low cumulative incidence of platelet concentrate transfusion dependence. Presence of SF3B1 mutation was a significant univariate predictor of overall survival, but become nonsignificant in the multivariate model. Although many factors also could affect survival, these results suggest that splicing factor mutations contribute to distinct MDS phenotypes, including patient characteristics and clinical courses.