中国人急性髓系白血病中IDH2基因突变及其临床特征分析

摘要

This study was purposed 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 patents.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 imunotype 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.%本研究检测192例急性髓系白血病(AML)患者IDH2基因突变并探讨其临床特征.提取AML患者初发时外周血或骨髓单个核细胞基因组DNA,通过PCR扩增产物直接测序法检测IDH2基因第4号外显子第140及第172氨基酸突变情况,同时也检测FLT3/ITD,NPM1,CEBPA,c-kit,IDH1,WT1及Dnmt3a突变.结果显示,192例急性白血病患者中共发现IDH2基因突变14例,突变率7.29％,其中R140Q突变9例,R140W突变1例,R172K突变4例.14例IDH2突变患者9例为AML-M5型白血病,与其他类型白血病相比有统计学差异(P＜0.05).IDH2突变组患者的年龄、性别、白细胞数、血小板数、血红蛋白水平、骨髓原始细胞数与IDH2野生型组相比均无统计学意义(P＞0.05).免疫分型中,IDH2突变较野生型易表达CD34(P ＜0.05)和CD13(P ＜0.05),不易表达CD36 (P＜0.05).IDH2突变在正常核型中的突变率为8.47％ (5/59),与异常核型组比较无明显差异(P＞0.05)；7例合并FLT3/ITD阳性,与野生型比较有无明显差异(P =0.018)；5例合并Dnmt3a突变,与野生型有明显差异(P=0.001)；不易合并IDH1突变发生(P＜0.05).14例突变中仅1例合并BCR/ABL融合基因,说明其不易发生伴融合基因(P＜0.05).7例IDH2 R140突变患者中6例达诱导后完全缓解,较野生型高,但无统计学意义.结论:IDH2基因R140及R172突变在中国人急性髓系白血病发病率为7.29％,以R140Q突变为主,其在CN-AML中发生率为7.81％；IDH2突变易发生在AML-M5中,易表达CD34和CD13,不易表达CD36,易合并FLT3/ITD,Dnmt3a突变发生,不易伴IDH1突变及融合基因发生,对完全缓解率无明显影响.