摘要
目的:探讨急性髓系白血病(AML)患者IDH1基因突变的发生率,并了解其临床特征及预后。方法:采用基因组DNA-PCR方法扩增IDH1基因4号外显子,应用基因测序分析其基因突变,同时检测NPM1、FLT3-TKD、FLT3-ITD、C-KIT、CEPBA、TET2及JAK2V617F及MLL突变情况,对患者进行随访判定其疗效和预后。结果:192例AML患者中,13例患者被检测到IDH1基因突变,突变率为6.77%[95%CI(5.70%-13.38%)]。IDH1基因突变测序图表现为双峰形,均为杂合突变,其中c.G395A(p.R132H)8例,c.C394T(p.R132C)4例,c.C394A(p.R132S)1例,R132H和R132C较为常见,13例均为错义突变,突变组的中位年龄为52岁,而未突变组中位年龄为40岁,两者存在着显著的差异(P=0.010)。IDH1突变在M1及M2中的发生率明显高于其他FAB亚型,两者在性别、初诊外周血白细胞计数、血红蛋白量、血小板计数、外周血原始细胞、骨髓原始细胞比例之间无明显的统计学差异。IDH1基因突变与NPM1基因突变有一定的相关性,但与FLT3-TKD、FLT3-ITD、C-KIT、TET2及JAK2V617F及MLL突变并无明显的相关性。此外,IDH1突变易发生于正常核型或预后中等风险核型的患者中,11例发生在正常核型患者中,突变率为10.28%,2例发生在核型异常患者中,有明显的统计学差异。在预后中等风险核型的AML患者中,IDH1突变组化疗完全缓解率(CR)低于未突变组,同时IDH1突变患者3年总生存率(OS)低于未突变患者,有明显统计学差异(P<0.05)。结论:IDH1基因突变更易存在于年龄偏大AML患者中,在预后中等风险核型患者中IDH1基因突变与患者的临床特点、疗效有一定相关性,提示是预后不良的分子学标志。
Objective : To evaluate the incidence rate of IDH1 in acute myeloid leukemia and analyze its effect on clincal characteristics and prognosis. Methods: Mononuclear cells in bone marrow samples were collected from 192 adult patients with newly diagnosed AML. Polymerase chain reaction( PCR) and direct sequencing were used to amplify exon 4 of IDH1 gene,the gene sequencing was used to analyze the gene mutations,at same time,the detection of NPM1,FLT3-TKD,FLT3-ITD,C-KIT,CEPBA,TET2 and JAK2V617 F and MLL mutations were carried out,the follow-up was used to determine its therapeutic efficacy and outcomes of patients. The clinical and laboratorial data of these cases were collected,and their clinical characteristics and prognosis were then analyzed. Results: Among the 192 AML patients,13 cases were detected with IDH1 gene mutation,the mutation rate was 6. 77% [95% CI( 5. 70%- 13.38%) ]. The sequencing chart of IDH1 gene showed double peaks,the mutations were heterozygous,out of them c. G395A( p. R132H) was found in 8 cases,c. C394 T was found in 4 cases( p. R132C),c. C394A( p. R132S) was found in 1 cases,R132 H and R132 C are common,13 cases showed missense mutation. The median age in mutation group was 52 years old,the median age in unnutation group was 40 years,there was significant difference between them( P = 0. 010). Mutation rate of IDH1 gene in M1 and M2 was significantly higher than that in other FAB subtypes.There were no significant difference in sex,newly diagnosed peripheral white blood cell count,hemoglobin,platelet count,peripheral blood and bone marrow original cell proportion of primitive cells between them. Mutation of IDH1 gene had certain correlation with NPM1 gene mutation,but no correlation with FLT3-TKD,FLT3-ITD,C-KIT,TET2 and JAK2V617F and MLL matations was found. In addition,the IDH1 mutation easily occurred in patients with normal karyotype or in patients with middle prognostic risk karyotype,IDH1 mutation occurred in 11 cases with normal karyotype,the mutation rate was 10. 28%,IDH1 mutation were
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2015年第5期1252-1257,共6页
Journal of Experimental Hematology
