急性髓系白血病患者IDH1和IDH2基因突变的检测及其临床意义  

Clinical significance of IDH1 and IDH2 mutations in patients with acute myeioid leukemia

作　　者：米瑞华 吕晓东 魏旭东 范瑞华 尹青松 胡杰英 王倩 宋永平 

机构地区：[1]郑州大学附属肿瘤医院血液科,450008 [2]郑州大学附属肿瘤医院中心实验室

出　　处：《中华血液学杂志》2011年第9期610-613,共4页Chinese Journal of Hematology

基　　金：河南省杰出青年基金（084100410019）;河南省医学攻关重点项目（200802016）

摘　　要：目的评估异柠檬酸脱氢酶1和2（IDH1和IDH2）基因突变在急性髓系白血病（AML）患者中的发生频率和对预后的影响，并探讨IDH突变与临床、细胞遗传学、分子危险度分层的关系。方法2009年9月至2011年1月收治的96例初治AML患者，采用RT—PCR扩增产物直接测序法检测IDH1及IDH2基因的突变情况，了解IDH突变阳性患者的临床特征。结果96例AML患者中检出IDHI突变患者14例（14．6％），突变位点包括国际上未见报道的P．P127和P．1130；检出IDH2突变2例（2．2％），突变位点为第140位氨基酸。14例IDH1突变阳性患者中10例为正常核型患者；2例IDH2突变阳性患者均为正常核型患者。IDH突变阳性的患者白细胞计数较高，血小板计数较低，但与野生型患者相比，差异无统计学意义（P〉0．05）。IDH2突变阳性患者年龄偏大。IDH突变阳性的患者表达HLA—DR、CD33、CD34、CD13抗原和具有缓解率低、复发率高的特点。结论IDH突变是AML患者常见的分子突变类型，并且是AML患者的不良预后因素。Objective To assess the frequencies and prognostic significance of the isocitrate dehy-drogenase 1 and 2（IDH1 and IDH2） mutations in acute myeloid leukemia（AML） and to explore their rele-vance to clinical, cytogenetic and molecular feature. Methods Genomic DNA from 96 newly dignosed AML patients from Sep. 2009 to Jan. 2011 was screened by RT-PCR and sequencing for IDH1 and IDH2 mutation. Results The prevalence of IDH1 （p. P127 and p. I130） and IDH2 mutations （p. R140） was 14.6% （ 14/ 96） and 2.17% （2/96） respectively. The IDH1 mutations of p. P127 and p. I130 were not reported so far in literature. Of 14 IDH1 mutation patients, 10 were with normal karyotype and the differences had statistical significance （P = 0. 021 ）. Two patients with IDH2 mutation were also with normal karyotype. IDH2 mutations were in older patients at diagnosis. Patients with IDH mutation had higher white blood cell counts, lower platelet counts, expression of HLA-DR, CD34, CD33 and CD13, lower remission rate and higher relapse rate. Conclusion IDH mutation is recurring genetic change in AML and indicates poor prognosis.

关 键 词：白血病 非淋巴细胞 急性 基因 IDH DNA突变分析 预后 

分 类 号：R733.71[医药卫生—肿瘤]