骨髓增生异常综合征SETBP1基因突变情况及其临床意义

Clinical significance of SETBP1 gene mutation in patients with myelodysplastic syndrome

目的:探讨骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者发生SET结合蛋白1(SET binding protein 1,SETBP1)基因突变的概率,以及突变患者的临床特征及其与预后的相关性。方法:2008年1月—2017年8月共收集201例初诊MDS患者骨髓标本,采用R显带技术进行常规核型分析;以基因组DNA为模板采用PCR扩增联合测序检测SETBP1、附加性梳样结构1(additional sex combs like 1,ASXL 1)、钙调磷酸酶B类蛋白(calcineurin B-like protein,CBL)、血小板生成素受体(myeloproliferative leukemia protein,MPL)、Janus激酶2(Janus kinase 2,JAK 2)和抑癌基因53(tumor suppressor 53,TP 53)基因的DNA序列;分析201例初诊MDS患者SETBP1基因突变情况及其临床意义。结果:201例MDS患者中25例患者存在SETBP1基因突变,突变率为12.4%。在多系发育异常的MDS患者中,SETBP1基因突变率明显高于其他WHO亚型。与野生型相比,SETBP1基因突变患者具有较高的白细胞计数,而血小板及血红蛋白均有降低的趋势;细胞遗传学方面,SETBP1基因突变患者多伴有-7/del(7q)或i(17)(q10)等染色体异常,合并ASXL 1基因突变(P值均<0.001),易于发生白血病转化;与野生组相比,SETBP1基因突变患者具有较低的中位生存期,中位无进展生存也存在缩短的趋势,提示预后较差。结论:SETBP1基因突变是MDS重要的分子标志物,伴有该基因突变的患者预后较差。

Objective： To investigate the mutation frequency of SET binding protein 1（SETBP1） gene in patients with myelodysplastic syndromes（MDS）, and the clinical characteristics and prognosis of patients with SETBP1 gene mutation.Methods： From January 2008 to August 2017, all of 201 patients with primary MDS were recruited in this study. The conventional karyotypeanalysis was carried out by R banding technique. Genomic DNA was extracted from mononuclear cells in bone marrow, and was amplified through allele-specific PCR. The sequences of SETBP1, additional sex combs like 1（ASXL 1）, calcineurin B-like protein（CBL）, myeloproliferative leukemia protein（MPL）, Janus kinase 2（JAK 2） and tumor suppressor 53（TP 53） genes were detected by DNA sequencing directly. The clinical and laboratory features of 201 patients with primary MDS were analyzed.Results： Among 201 MDS patients, SETBP1 gene mutation was found in 25 patients, with a mutation rate of 12.4%. The mutation rate of SETBP1 gene in MDS patients with multilineage dysplasia was higher than that in WHO subtypes of MDS patients. Compared with the wild type of MDS patients, the patients with SETBP1 gene mutation had higher count of leukocyte, lower trend of the platelet and hemoglobin. In the cytogeneticaspect, the patients with SETBP1 gene mutation were often associated with chromosomal abnormalities such as-7/del（7 q） or i（17）（q10）, accompanied with ASXL 1 gene mutation（both P 〈0.001）, and more prone to transfer to leukemia.Compared with the wild type of MDS patients, the patients with SETBP1 gene mutation had shorter median survival time and the lower trend of the median progression-free survival, suggesting they had a poor prognosis.Conclusion： SETBP1 gene mutation is an important molecular marker of MDS, and the patients with SETBP1 gene mutation have a poor prognosis.