急性髓系白血病患者ND4基因突变情况分析  

Analysis of ND4 gene mutations in acute myelogenous leukemia

作　　者：乔纯[1] 周琛[2] 张苏江[1] 郭睿[1] 张凡[2] 钱思轩[1] 环亚红[2] 宋艳智 廖海英[2] 李翠萍[2] 夏素琴[2] 隋雪梅[2] 卢应连 李建勇[1] 李东[2] 

机构地区：[1]南京医科大学第一附属医院、江苏省人民医院血液科,210029 [2]南京明基医院、南京医科大学附属医院血液科

出　　处：《中华血液学杂志》2014年第8期708-712,共5页Chinese Journal of Hematology

基　　金：南京医科大学科技发展基金（2011NJMU223）

摘　　要：目的 探讨急性髓系白血病（AML）患者ND4基因突变情况及临床意义.方法 采用PCR扩增产物直接测序法检测121例AML患者ND4基因的突变情况,分析突变阳性患者的临床特征.结果 121例初诊AML患者,其中男58例,女63例,中位年龄为49 （10～86）岁,ND4突变阳性患者为8例（6.6％）.突变均为错义突变,类型包括A131V 3例,A404T 2例,F149L、G242D、Y409H各1例.ND4基因突变型患者和野生型患者相比,性别、年龄、WBC、HGB 、PLT、骨髓原始细胞比例、免疫表型等差异均无统计学意义（P＞0.05）.具有突变的患者染色体核型预后相对良好,差异具有统计学意义（P=0.049）.突变患者与野生型患者相比,FLT3基因内部串联重复序列（FLT3-ITD）、核仁磷酸蛋白（NPM1）、CCAAT/增强子结合蛋白α（CEBPA）、c-KIT和DNMT3A等基因突变发生率差异均无统计学意义（P＞0.05）.ND4基因突变型和野生型患者的中位总生存期均未达到,中位无复发生存期分别为未达到和29（2～53）个月,差异均无统计学意义（P＞0.05）.ND4基因突变型和野生型患者的完全缓解率和复发率差异均无统计学意义（P＞0.05）.结论 ND4基因突变是一种新型的分子突变,在AML患者预后判断中可能具有重要意义,但线粒体功能障碍是如何致病的仍需继续研究.Objective To investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia （AML） patients with ND4 mutations.Methods Using PCR combined with directly sequencing,we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features.Results There were 58 male patients and 63 female patients （median age 49 years,10-86 years）.Eight of 121 patients （6.6％） with de novo AML were found harboring missense mutation of ND4 gene,including 3 patients with A131V （3/8,37.5％）,2 patients with A404T （2/8,25％）,1 patient with F149L（1/8,12.5％）,l patient with G242D（1/8,12.5％） and 1 patient with Y409H（1/8,12.5％）,respectively.Patients with ND4 mutations were associated with good karyotype （P=0.049）,regardless of gender,age,white blood cell,hemoglobin,platelet,blast cells of bone marrow or immunophenotype （P＞0.05）.There were no statistical significance in mutations of FLT3-ITD,NPM1,CEBPA,c-KIT and DNMT3A between patients with ND4 mutation and wild-type（wt）ND4 （P＞0.05）.The median overall survival of patients with ND4 mutations and wt ND4 were all not reached.The median relapse-free survival were not reached and 29 （2-53） months,respectively （P＞0.05）.There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups （P＞0.05）.Conclusion It was concluded that novel ND4 mutations could be found in de novo AML patients,especially in patients with good karyotype.Thus,ND4 mutations might play an important role in AML prognosis.However,whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.

关 键 词：基因 ND4 白血病 髓样 急性 DNA突变分析 DNA 线粒体 

分 类 号：R733.71[医药卫生—肿瘤]