JAK2 V617F、DNMT3A、NPM1和FLT3-ITD基因突变与骨髓增殖性肿瘤预后的相关性分析  

A correlation analysis between gene mutation of JAK2 V617F,DNMT3A,NPM1 and FLT3-ITD and the prognosis of MPN

作　　者：张叶华[1] 郭素丽[1] ZHANG Ye-hua;GUO Su-li(Department of Hematology,Xingtai People's Hospital,Xingtai 054001,China)

机构地区：[1]邢台市人民医院血液内科,河北邢台054001

出　　处：《中国医学装备》2019年第2期37-42,共6页China Medical Equipment

基　　金：邢台市科技支撑项目(2015ZC091)"骨髓病理;JAK2/V617F基因突变;CALR-CN09突变在骨髓增殖性疾病中的临床研究"

摘　　要：目的:探讨JAK2 V617F、DNMT3A、NPM1和FLT3-ITD基因突变与骨髓增殖性肿瘤(MPN)预后的相关性。方法:收集80例MPN患者外周血及骨髓标本,根据核型分析结果将其分为预后良好组(36例)、中度风险组(22例)及不良风险组(22例)。所有患者行细胞遗传学及染色体核型分析,使用下一代测序(NGS)技术检测与MPN发病相关的JAK2 V617F、DNMT3A、NPM1及FLT3-ITD等基因。对患者均随访3年,统计其生存期,分析JAK2 V617F、DNMT3A、NPM1和FLT3-ITD基因突变与MPN预后的相关性。结果:80例MPN患者中有73例(占91%)至少发生1个基因突变,多基因(≥2)突变占61%。JAK2 V617F在MPN亚型PV、ET及PMF中阳性突变率分别为89.47%、74.19%和50%;DNMT3A、NPM1和FLT3-ITD存在很低突变率,但在慢性髓细胞白血病(CML)中存在较高阳性突变率。CML中仅检测到1例JAK2 V617F基因突变。JAK2 V617F、DNMT3A、NPM1和FLT3-ITD基因突变阳性与阴性患者总体生存期比较均无差异,与MPN患者预后无明显相关性。MPN亚型病例中,JAK2V617F阳性PMF患者同时伴NPM1基因突变的患者与其他突变类型比较,中位生存期明显短于其他突变类型患者,差异均有统计学意义(t=11.086,P<0.05);CML中度风险组中,FLT3-ITD同时伴NPM1或DNMT3A突变,与其他组比较,差异均有统计学意义(t=9.637,P<0.05)。结论:JAK2 V617F突变在MPN患者中存在较高突变率,但与预后无关;在JAK2V617F阳性同时伴NPM1基因突变的PMF患者中,转为白血病存在较高概率,且预后不良。DNMT3A、NPM1和FLT3-ITD在MPN患者PV、ET及PMF亚型中突变率低,但在CML患者中NPM1和FLT3-ITD存在较高突变率;FLT3-ITD同时伴NPM1或DNMT3A突变,且预后不良。在中度风险组患者中可产生预后效应。Objective:To investigate the correlation between gene mutations of JAK2 V617F,DNMT3A,NPM1 and FLT3-ITD and the prognosis of myeloproliferative neoplasms(MPN).Methods:After these specimens of peripheral blood and marrow of 80 patients with MPN were selected,they were divided into favorable prognosis group(36 cases),moderate risk group(22 cases)and badness risk group(22 cases)according to the results of karyotype analysis.All of patients were analyzed by cytogenetics and karyotype,and the next generation sequencing(NGS)technique was used to detect JAK2 V617F,DNMT3A,NPM1 and FLT3-ITD that were relevant with the morbidity of MPN.And these patients were followed up for 3 years and their lifetimes were analyzed by using statistic method.And then the correlation of gene mutation of JAK2 V617F,DNMT3A,NPM1 and FLT3-ITD and the prognosis of MPN were further analyzed.Results:In these 80 MPN patients,there were 73 cases(91%)occurred one gene mutation at least,and the rate of polygenic mutations(≥2)were 61%.The positive mutation rates of JAK2 V617F in subtype PV,ET and PMF of MPN were 89.47%,74.19%and 50%,respectively.There were very low mutation rates in DNMT3A,NPM1 and FLT3-ITD,while the higher positive mutation rate were occurred in CML.Only 1 patients with CML occurred JAK2 V617F gene mutation.The differences of total lifetime between patients with gene mutation positive and one with gene mutation negative about JAK2 V617F,DNMT3A,NPM1 and FLT3-ITD were no significant.And there was no significant correlation between these mutations and prognosis of patients with MPN.In these cases of MPN subtype,the median survival of patients with PMF and JAK2 V617F positive who accompanied with NPM1 gene mutation was significantly shorter than that of patients with other mutation type(t=11.086,P<0.05).The differences of mutations that FLT3-ITD accompanied NPM1 or DNMT3A between CML group with moderate risk and other groups was significantly(t=9.637,P<0.05).Conclusion:JAK2 V617F mutation exists higher mutation rate in patients with MPN,

关 键 词：新一代测序 基因突变 骨髓增殖性肿瘤 染色体核型 预后 相关性 

分 类 号：R733.3[医药卫生—肿瘤]