Shingai Naoki, Harada Yuka, Iizuka Hiroko, Ogata Yosuke, Doki Noriko, Ohashi Kazuteru, Hagihara Masao, Komatsu Norio, Harada Hironori
Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.
Department of Clinical Laboratory Medicine, Bunkyo Gakuin University, Tokyo, Japan.
Int J Hematol. 2018 Dec;108(6):598-606. doi: 10.1007/s12185-018-2551-y. Epub 2018 Oct 23.
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.
60%-70%的骨髓增生异常综合征（MDS）患者存在剪接因子基因突变。我们研究了剪接因子基因突变对MDS诊断、患者特征及预后的影响。共纳入106例MDS患者。按照2017年世界卫生组织（WHO）分类，伴有环形铁粒幼细胞的MDS患者比例（14.15%）显著高于按照2008年WHO分类的伴有环形铁粒幼细胞的难治性贫血患者比例（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和11例SRSF2），且这些突变相互排斥。不同突变患者的平均红细胞体积、血小板计数、骨髓髓系与红系比例及巨核细胞计数存在显著差异。SRSF2突变与红细胞输注依赖的高累积发生率相关，而SF3B1突变与血小板浓缩物输注依赖的低累积发生率相关。SF3B1突变的存在是总生存的显著单因素预测指标，但在多因素模型中无显著性意义。尽管许多因素也可影响生存，但这些结果表明剪接因子突变促成了不同的MDS表型，包括患者特征和临床病程。
