Luo Li-Qing, Peng Zhen-Yi, Liu Xiao, Yu Wen-Zheng
Department of Hematology, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China.
Department of Thyroid & Breast Surgery,, Affiliated Hospital of Binzhou Medical College, Binzhou 256603, Shandong Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Aug;27(4):1077-1082. doi: 10.19746/j.cnki.issn.1009-2137.2019.04.014.
To analyze the prevalence, clinical characteristics and prognostic significance of the isocitrate dehydrogenase 2(IDH2) mutations in patients with acute myeloid leukemia(AML).
The bone marrow samples of 223 patients with newly diagnosed AML confirmed by MICM typing from January 2015 to October 2018 were collected. The mutation of exon 4 of IDH2 gene was detected by direct sequancing of PCR product; the incidence and types of IDH2 gene mutation in AML patients were analyzed; the clinical characteristics of AML patients with IDH2 gene mutation were analyzed and the therapeutic efficacy for these patients was evaluated.
In a cohort of 223 AML patients, mutations were detected in 23(10.31％) patients, among them, 15 with R140Q mutations(65.22%) , 6 with R172K mutations(26.09%) and 2 with R140W mutations(8.70%). The median age in IDH2 mutated group was older than that in non.mutated group(P=0.008). The platelet level at initial diagnosis in IDH2 mutated group was higher than that in non.mutated group(P=0.010). There was no significant statistical difference between IDH2 mutated group and non.mutated group in FAB subtypes of AML(P>0.05). But the rate of IDH2 mutation in M4 and M5 was higher. The rate of IDH2 mutations was higher in AML with normal karyotype and in AML with NPM1 mutations. R140Q mutations associated with NPM1 mutations(χ=8.481，P=0.004), but R172K mutations not associated with NPM1 mutation(P>0.05). IDH2 mutated patients had a lower complete remission rate than non.mutated patients(57.14% vs 80.46%, χ=5.927，P=0.015). The complete remission rate of R140Q mutated patients was not significantly statistically different from non.mutated patients. The complete remission rate of R172K mutated patients was very significantly lower than non.mutated patients(χ=7.734，P=0.005). In the patients without NPM1 mutation, the 2 years overall survival in IDH2 mutated group was lower than in non.mutated group(36.36% vs 66.40%,χ=3.958，P=0.047), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In all patients, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(50% vs 66.88%,P>0.05), the 2 years overall survival of R172K mutated group was significantly lower than non.mutated group(although P>0.05). In the patients with normal karyotype or with mutated NPM1, the 2 years overall survival between IDH2 mutated group and non.mutated group was not statistically different(P>0.05).
IDH2 gene mutations are more common in AML patients at older age, higher platelets level and normal karyotype. The rate of IDH2 mutation in M4 and M5 is higher. IDH2 gene mutations associate with NPMl gene mutations, but R172K mutations not associates with NPM1mutation. IDH2 gene mutations associate with prognosis of AML patients, R140Q mutations have no effect on prognosis of patients, but R172K mutations may be the molecular markers for poor prognosis in AML patients.
分析急性髓系白血病（AML）患者异柠檬酸脱氢酶2（IDH2）突变的发生率、临床特征及预后意义。
收集2015年1月至2018年10月间经MICM分型确诊的223例初诊AML患者的骨髓样本。采用PCR产物直接测序法检测IDH2基因第4外显子的突变情况；分析AML患者IDH2基因突变的发生率及类型；分析IDH2基因突变AML患者的临床特征并评估其治疗效果。
在223例AML患者队列中，23例（10.31％）检测到突变，其中15例为R140Q突变（65.22%），6例为R172K突变（26.09%），2例为R140W突变（8.70%）。IDH2突变组的中位年龄高于未突变组（P=0.008）。IDH2突变组初诊时的血小板水平高于未突变组（P=0.010）。AML的FAB亚型在IDH2突变组和未突变组之间无显著统计学差异（P>0.05）。但M4和M5中IDH2突变率较高。核型正常的AML及伴有NPM1突变的AML中IDH2突变率较高。R140Q突变与NPM1突变相关（χ=8.481，P=0.004），但R172K突变与NPM1突变无关（P>0.05）。IDH2突变患者的完全缓解率低于未突变患者（57.14%对80.46%，χ=5.927，P=0.015）。R140Q突变患者的完全缓解率与未突变患者无显著统计学差异。R172K突变患者的完全缓解率显著低于未突变患者（χ=7.734，P=0.005）。在无NPM1突变的患者中，IDH2突变组的2年总生存率低于未突变组（36.36%对66.40%，χ=3.958，P=0.047），R172K突变组的2年总生存率显著低于未突变组（尽管P>0.05）。在所有患者中，IDH2突变组和未突变组的2年总生存率无统计学差异（50%对66.88%，P>0.05），R172K突变组的2年总生存率显著低于未突变组（尽管P>0.05）。在核型正常或伴有NPM1突变的患者中，IDH2突变组和未突变组的2年总生存率无统计学差异（P>0.05）。
IDH2基因突变在年龄较大、血小板水平较高及核型正常的AML患者中更常见。M4和M5中IDH2突变率较高。IDH2基因突变与NPMl基因突变相关，但R172K突变与NPM1突变无关。IDH2基因突变与AML患者的预后相关，R140Q突变对患者预后无影响，但R172K突变可能是AML患者预后不良的分子标志物。
