DNMT3A基因对非M3型急性髓系白血病患者预后的预测价值

目的通过分析非M3型急性髓系白血病(AML)患者的临床和实验室资料,进一步阐明DNMT3A基因突变在非M3型AML患者预后中的意义及其影响AML发生发展的可能机制。方法采用R语言3.5.1版本RTCGAToolbox包下载癌症基因组图谱数据库180例非M3型AML患者临床及突变信息,数据为开放性数据。将患者按照突变状态进行分组,比较各组患者外周血白细胞计数、骨髓原始细胞比例、无事件生存期以及总体生存期有无差别。将患者按照年龄分为<60岁组和≥60岁组,使用Kaplan-Meier方法绘制生存曲线,并运用Log-rank检验进行<60岁和≥60岁患者、DNMT3A突变组及野生组患者生存率的比较。采用Cox比例风险模型进行DNMT3A突变和其伴随突变及年龄分层等因素对患者总体生存期的单因素和多因素分析。结果共纳入非M3型AML患者180例,DNMT3A突变组与野生组患者临床特征比较发现突变组白细胞计数显著高于野生组(Z=-2.606,P=0.009),且DNMT3A突变多见于中危患者。值得注意的是,DNMT3A突变常伴随FLT3(P=0.025)、NPM1(P<0.001)、IDH1(P=0.002)突变的发生,且DNMT3Awt/FLT3wt组无事件生存期显著高于DNMT3Amut/FLT3mut组(11.00个月vs 6.15个月,P=0.005),而与DNMT3Amut/FLT3wt、DNMT3Awt/FLT3mut组之间的差异无统计学意义。Cox多因素分析结果显示,高龄是AML患者总体生存的独立危险因素(HR=2.974,95%CI:1.966~4.500,P<0.001);另外,DNMT3A R882突变是AML患者预后不良的独立预测因子(HR=1.937,95%CI:1.179~3.182,P=0.009)。结论高龄(≥60岁)和DNMT3A R882突变为预后不良的独立预测因子。DNMT3Amut/FLT3mut亚型与DNMT3Awt/FLT3wt、DNMT3Amut/FLT3wt、DNMT3Awt/FLT3mut相比,临床预后更差。

Prognostic value of DNMT3A gene in patients with non-M3 acute myeloid leukemia

ObjectiveTo further clarify the significance of DNMT3A gene mutations in the prognosis of acute myeloid leukemia (AML) patients and the possible mechanism for its impact on the development of AML by analyzing the clinical and laboratory data of non-M3 AML patients. MethodsR language software was used to download the clinical and mutation data of non-M3 AML patients from The Cancer Genome Atlas (TCGA). The patients were divided into groups according to the mutation status, and the differences of peripheral blood leukocyte count (WBC), proportion of bone marrow primordial cells, event free survival, and overall survival (OS) were compared. The patients were also divided into groups according to their age and survival curves were plotted using the Kaplan-Meier method. The log-rank test was used to compare the survival rate between patients younger than 60 years old and those older than 60 years old, as well as between the DNMT3A mutation group and the wild type group. Cox proportional risk model was used to conduct single- and multiple-factor analyses of the impact of factors such as DNMT3A mutation, its accompanying mutation, and age stratification on the OS of patients. ResultsA total of 180 non-M3 AML patients were included. WBC in the mutation group was significantly higher than that in the wild type group (Z=-2.606, P=0.009), and the mutation of DNMT3A was more common in the middle risk patients. Mutations of DNMT3A often occurred together with FLT3, NPM1, and IDH1 mutations. The event-free survival of the DNMT3Awt/FLT3wt group was significantly longer than that of the DNMT3Amut/FLT3mut group (11.00 months vs 6.15 months, P=0.005), but had no significant difference compared with that of the DNMT3Amut/FLT3wt or DNMT3Awt/FLT3mut group. Cox multivariate analysis showed that advanced age was an independent risk factor for OS of AML patients (P<0.001). DNMT3A R882 mutation was an independent predictor of poor prognosis in AML patients (P=0.009). ConclusionAge over 60 years and DNMT3AR882 mutation are independent predictors of poor prognosis. Compared with patients with DNMT3Awt/FLT3wt, DNMT3Amut/FLT3wt, and DNMT3Awt/FLT3mut, patients with DNMT3Amut/FLT3mut have worse clinical consequences.