急性髓系白血病患者IDH1及IDH2基因突变及临床特征分析  

Clinical characteristics in adult acute myeloid leukemia with isocitrate dehydrogenase gene mutation

作　　者：王蓉娴[1] 吴德沛[1] 陈苏宁[1] 何军[1] 徐杨[1] 王秀丽[1] 尹佳[1] 田竑[1] 田孝鹏[1] 孙爱宁[1] 

机构地区：[1]苏州大学附属第一医院血液科江苏省血液研究所卫生部血栓与止血重点实验室,215006

出　　处：《中华医学杂志》2013年第10期751-755,共5页National Medical Journal of China

基　　金：江苏省自然科学基金（BK2010206）;江苏省高校优势学科建设工程资助项目

摘　　要：目的探讨急性髓系白血病（AML）患者异柠檬酸脱氢酶（IDH）1及IDH2基因突变的发生率，并探讨其临床特征及意义。方法选取2005年2月至2011年3月经MICM分型确诊的570例初治AML患者，采用骨髓单个核细胞基因组DNA，PCR方法扩增IDH1、IDH2基因4号外显子，基因测序检测IDH1 R132及IDH2R140／R172基因突变，分析患者临床特征并判定其疗效。结果570例AML患者中90例检测到IDH基因突变，突变率为15．79％，其中IDH1突变27例（4．74％），IDH2突变63例（11．05％）。未发现有患者同时获得IDH1和IDH2突变。IDH突变与FAB分型中AML-M1显著相关（P〈0．01）；突变组年龄、初诊外周血血小板计数与未突变组比较，差异有统计学意义（中位数：53岁比40岁，52×10^9／L比31×10^9／L，均P〈0．01）；IDH基因突变与正常核型、NPM1基因突变，尤其是NPM1基因突变未伴FLT3．ITD基因突变的基因型相关，但与WT1、FLT3-TKD及MLL．PTD突变无明显的相关性。在非M3型患者中，突变组的化疗完全缓解率低于未突变组（58．1％比77．9％）．差异有统计学意义（P〈0．05）。在不伴NPM1基因突变的患者或在正常核型的亚群中，IDH基因突变者预计2年总生存率低于该基因未突变者（28．4％比51．3％，P〈0．01）。结论IDH基因突变更易存在于年龄偏大的AML患者中，IDH突变与临床特点、疗效具有一定相关性，提示是预后不良的分子学标志。Objective To explore the prevalence and clinical characteristics of isocitrate dehydrogenase （IDH）1 R132 and IDH2 R140/R172 gene mutations in acute myeloid leukemia （AML） patients. Methods Polymerase chain reaction （PCR） and direct sequencing were used to sequence exon 4 of IDH gene in 570 AML patients from 2005 to 2011. Results In a cohort of 570 patients, AML IDH gene mutation was found in 90 （ 15.79% ） patients. IDH1 and IDH2 mutations were detected in 27 （4. 74% ） patients and 63 （11.05%） patients respectively. None of them had the combined mutations of IDH1 and IDH2. The highest frequency of IDH mutations was found in AML M1 （according to the FAB scheme） compared with all other subtypes （P 〈 0. 01 ）. The median age was 53 years in mutated group versus 40 years in wild-type group （ P = 0. 010）. Mutated and wild-type groups had no significant difference in gender, white blood cell count at diagnosis, hemoglobin count and bone marrow blast percentage, excepting for blood platelets level （median 52×10^9/L vs 31 ×10^9/L, P 〈 0. 01 ）. IDH gene mutations were associated with cytogenetically normal （CN）-AML, NPM1 mutations and particularly with the genotype of mutated NPM1 without FLT3-ITD-IDH gene mutations had no significant correlation with WT1, FLT3-TKD and MLL-PTD mutations. IDH mutated patients had a lower complete remission rate than unmutated in non-M3 patients （58.1% vs 77.9%, P 〈 0.05 ）. And the patients with mutant IDH gene were associated with a shorter overall survival（28.4% vs 51.3%, P 〈 0.01 ）. Conclusion IDH gene mutations are more prevalent inelder AML patients and it may constitute a molecular marker for a poor prognosis in AML.

关 键 词：白血病 髓样 急性 DNA突变分析 预后 异柠檬酸脱氢酶基因 

分 类 号：R733.71[医药卫生—肿瘤]