Shang Zhen, Wang Di, Xiao Ming, Wang Jue, Li Tong-Juan, Zhao Yue-Chao, Li Chun-Rui, Zhou Jian-Feng
Department of Hematology, Huazhong University of Science and Technology, Hubei Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Jun;21(3):607-12. doi: 10.7534/j.issn.1009-2137.2013.03.014.
This study was purpose to analyze the frequency and of isocitrate dehydrogenase 2 (IDH2) gene mutation in acute myeloid leukemia (AML) and its clinic significance. The multiplex polymerase chain reaction (PCR) and sequencing were performed to screen 192 AML patients for exon 4 of the IDH2 gene. FLT3, NPM1, CEBPA, c-kit and WT1 mutations were also included in analysis. The results showed that IDH2 mutation was found in 14 (7.29%) of 192 patients. There were 9 AML patients with R140Q mutation, 1 patient with R140W mutation, and 1 patient with R172K mutation. IDH2 aberrations significantly more were detected in French-American-British (FAB) M5 (P < 0.005) than other types. There was no statistical difference in age, sex, WBC, platelet count, bone marrow blasts count, hemoglobin as compared with IDH2 wild-type. For immunotype analysis, IDH2 mutation patients were more likely to express CD34 and CD13, less CD36. IDH2 mutation combined with FLT3/ITD mutation was found in 7 cases, with CEBPA mutation in 4 cases, with NPM1 mutation in 4 cases, with Dnmt3a mutation in 5 cases, neither with c-kit, IDH1 or WT1 mutation for no one, which revealed a significant interaction between IDH2 mutation and the FLT3/ITD positive genotype, Dnmt3a mutated, and IDH1 wild-type. IDH2 mutation was detected in 5 (8.47%) of 59 CN-AML. There was no significant difference of IDH2 mutation incidence between the normal and abnormal karyotype. The CR rate was higher in IDH2 R140 mutated patients than wild-type ones, but there was no significant in the two group. It is concluded that the rate of IDH2 mutation is 7.29% in Chinese AML patients and 7.81% in CN-AML. IDH2 mutation is significantly associated with AML-M5, FLT3/ITD, Dnmt3a, IDH1 wild-type and fusion gene wild-type, but not with age, leucocyte and platelet counts in peripheral blood, karyotype, NPM1, CEBPA, c-kit or WT1 mutation. And IDH2 R140 mutation has no impact on CR rate.
本研究旨在分析急性髓系白血病(AML)中异柠檬酸脱氢酶2(IDH2)基因突变的频率及其临床意义。采用多重聚合酶链反应(PCR)和测序技术对192例AML患者的IDH2基因第4外显子进行筛查。分析中还纳入了FLT3、NPM1、CEBPA、c-kit和WT1基因突变情况。结果显示,192例患者中有14例(7.29%)检测到IDH2基因突变。其中9例AML患者为R140Q突变,1例为R140W突变,1例为R172K突变。与其他类型相比,法国-美国-英国(FAB)M5型中检测到的IDH2异常明显更多(P<0.005)。与IDH2野生型相比,在年龄、性别、白细胞、血小板计数、骨髓原始细胞计数、血红蛋白方面无统计学差异。免疫表型分析显示,IDH2基因突变患者更易表达CD34和CD13,而CD36表达较少。发现7例IDH2基因突变合并FLT3/ITD突变,4例合并CEBPA突变,4例合并NPM1突变,5例合并Dnmt3a突变,无一例合并c-kit、IDH1或WT1突变,这表明IDH2基因突变与FLT3/ITD阳性基因型、Dnmt3a突变和IDH1野生型之间存在显著相互作用。59例核型正常的AML(CN-AML)患者中有5例(8.47%)检测到IDH2基因突变。正常核型与异常核型的IDH2基因突变发生率无显著差异。IDH2基因R140突变患者的完全缓解(CR)率高于野生型患者,但两组间无显著差异。结论是,中国AML患者中IDH2基因突变率为7.29%,CN-AML患者中为7.81%。IDH2基因突变与AML-M5、FLT3/ITD、Dnmt3a、IDH1野生型和融合基因野生型显著相关,但与年龄、外周血白细胞和血小板计数、核型、NPM1、CEBPA、c-kit或WT1基因突变无关。且IDH2基因R140突变对CR率无影响。