伴RUNX1突变的MDS患者临床特征及预后分析

Clinical Characteristics and Prognosis Analysis of MDS Patients with Mutated RUNX1.

目的探究RUNX1突变在骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者中的临床特征及预后影响。方法收集2009年1月~2021年2月于上海交通大学医学院附属第六人民医院初诊的661例MDS患者的骨髓标本,采用二代测序检测一系列基因突变,重点回顾性分析RUNX1患者的临床特征、共同突变表达谱及预后意义。结果661例MDS患者中,65例伴有RUNX1突变。与无RUNX1突变患者比较,RUNX1突变患者骨髓原始细胞比例增加(P<0.001),其预后分层在修订国际预后积分系统(Revised International Scoring System,IPSS-R)较高危组和IPSS-M(IPSS-Molecular)高危/极高危组均占比较高(P<0.001)。59例RUNX1突变患者同时存在其他基因突变,突变频率较高的是ASXL1(24.62%)、TET2(24.62%)、EZH2(21.54%)和U2AF1(21.54%)等,主要为表观遗传学基因(63.62%)和剪切子基因(38.46%)。相关性分析发现,RUNX1突变与EZH2、PHF6和U2AF1突变呈正相关(Q<0.05)。RUNX1突变患者总体生存期较短(16个月vs 47个月,P<0.001),急性髓系白血病(acute myeloid leukemia,AML)转化风险较高(P<0.001),但在RUNX1主克隆和亚克隆突变间患者总体生存差异无统计学意义。结论RUNX1突变在MDS患者中发生率较高,且常伴有表观遗传学基因和剪切子基因突变。RUNX1突变预示着较短的总体生存期和较高的AML转化风险。

Objective To investigate the clinical characteristics and prognostic effects of myelodysplastic syndromes(MDS)patients with mutated RUNX1.Methods Bone marrow samples from 661 newly diagnosed MDS patients in the Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected.A series of gene mutations were detected by next generation sequencing(NGS).The clinical characteristics,common mutation profile and prognostic significance of patients with mutated RUNX1 were analyzed retrospectively.Results Of the 661 patients with MDS,65had RUNX1mutation.Compared with patients without RUNX1mutation,patients with RUNX1mutation had an increased proportion of bone marrow blasts(P<0.001),and were more concentrated in higher-risk group of Revised International Scoring System(IPSS-R,P<0.001)and high/very high risk group of IPSS-Molecular(IPSS-M,P<0.001).59 patients with RUNX1mutation also had other mutations,such as ASXL1(24.62%),TET2(24.62%),EZH2(21.54%)and U2AF1(21.54%),which mainly belong to epigenetic genes(63.62%)and splicing genes(38.46%).Further,correlation analysis showed that RUNX1mutation were positively correlated with EZH2,PHF6 and U2AF1mutations(Q<0.05).Patients with RUNX1mutation had shorter overall survival(16months vs 47months,P<0.001)and higher risk of acute myeloid leukemia(AML)transformation than wild-type RUNX1(P<0.001).However,there was no significant differences in overall survival between RUNX1 funding clones and subclones.Conclusion RUNX1 mutations have a high incidence in MDS patients,which are often accompanied by mutated epigenetic genes and splicing genes.RUNX1 mutations predicts shorter overall survival and higher risk of AML transformation.