骨髓增生异常综合征患者基因突变及临床特征分析

Relationship between clinical features and mutations of MDS-related genes in patients with myelodysplastic syndrome

目的探讨骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者基因突变谱和临床特征及两者间的相关性。方法在62例初发MDS患者中利用二代测序技术对34种髓系高频基因突变情况进行检测;统计分析突变阳性组和阴性组在染色体核型、临床特征、实验室检查结果、MDS亚型、IPSS-R积分等方面的差异。结果62例MDS患者中83.87%(52例)的患者可检测到至少一种基因突变(NGS阳性组),10例患者34种基因均无突变(NGS阴性组)。29.03%(18例)的患者可检测到3种以上基因突变。突变频率最高的基因是表观遗传相关基因,其中TET2基因突变率最高(19.35%,12/62),其次为DNMT3A(17.1%,11/62)。NGS突变阴性组的白细胞总数及中性粒细胞数均明显高于NGS突变阳性组。TET2突变组的血红蛋白水平明显高于TET2非突变组及NGS阴性组,而异常核型发生率要显著低于TET2非突变组及NGS阴性组。DNMT3A突变组骨髓原始细胞比例、IPSS-R评分均低于DNMT3A非突变组,DNMT3A突变组在LDH>250 U/L的发生率及IPSS-R评分方面均明显低于NGS阴性组。TP53突变组血小板计数及血清铁水平明显低于TP53非突变组,而LDH水平和IPSS-R明显高于TP53非突变组。TP53突变组血小板计数、白细胞计数及血清铁水平均明显低于NGS阴性组。结论MDS患者基因突变发生率高,基因突变的发生导致在血常规、核型异常发生率、骨髓原始细胞比例、IPSS-R评分等方面有不同的差异表现。

Objective To explore the relationship between the mutations of MDS-related genes and clinical features in patients with myelodysplastic syndrome(MDS).Methods The next generation sequencing technique was used to detect mutations of 34 MDS-related genes in 62 MDS patients.The karyotype,clinical features,laboratory test results,MDS subtype,IPSS-R scores were analyzed and compared between the mutation positive and negative groups.Results Among 62 MDS patients,52(83.87%)harbored at least one mutation in MDS-related genes(NGS positive group)and 29.03%had more than three mutations;while 10 patients had no mutations(NGS negative group).The epigenetic regulator genes had the highest mutation frequency,especially for the TET2 gene(19.35%,12/62)and DNMT3A gene(17.1%,11/62).The WBC and neutrophils counts were significantly higher in the patients of NGS negative group than those of the NGS positive group.The hemoglobin level in TET2 mutation group was significantly higher than that in TET2 non-mutant group and NGS negative group,while the frequency of abnormal karyotype was significantly lower than that in TET2 non-mutant group and NGS negative group.The percentage of blasts in the bone marrow and IPSS-R score in the DNMT3A mutant group were significantly lower than those in the DNMT3A non-mutant group.The frequency of LDH>250 U/L and the IPSS-R score in the DNMT3A mutant group were significantly lower than those in the NGS negative group.The platelet count and serum iron level in the TP53 mutation group were significantly lower than those in the TP53 non-mutant group,while the LDH level and IPSS-R were significantly higher than those in the TP53 non-mutant group.The platelet count,white blood cell count and serum iron level in the TP53 mutation group were significantly lower than those in the NGS negative group.Conclusion MDS patients had a high-frequency of MDS-related gene mutations,which are associated with clinical features such as blood routine,karyotype,ratio of bone marrow blasts and IPSS-R score.