摘要
目的:采用二代测序(next generation sequencing,NGS)检测AML/MDS相关基因突变,分析各基因在AML和MDS中的突变情况及NGS的敏感性,评估基因突变作为MRD监测及疾病进展预测的可行性。方法:标本取自2015年8月至2016年6月在哈尔滨血液病肿瘤研究所诊治的初发AML(68例)和MDS(57例)患者,采用上海源奇生命科技有限公司的AML/MDS-NGS芯片检测22个相关基因突变。结果:TET2是AML(55.9%)和MDS(56.1%)中突变率最高的基因,在AML中突变率次之的基因为CEBPA(11.8%)、DNMT3A(7.4%)、C-KIT(7.4%)和FLT3(7.4%),在MDS中为U2AF1(10.5%)和SRSF2(10.5%)。除TP53和CEBPA基因外,其他基因均有特定突变位点。复检的5例AML患者缓解时与初发时相比,FLT3、C-KIT和CEBPA基因突变均转阴,而伴随的TET2基因突变率无明显变化,而5例MDS患者缓解与初发时各基因的突变率无明显变化,其中3例MDS患者发生了疾病进展,疾病进展时出现新的基因突变,但缓解后基因突变率也无明显变化。结论:AML和MDS中均有其特定突变基因和突变位点,一些基因突变如CEBPA等可作为AML中MRD监测的有效指标,但在MDS中仅可用于预后及疾病进展评估。
Objective： To detect the mutations of AML/MDS-related genes by using next generation sequencing（ NGS）,to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS,and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. Methods： The specimens were collected from primary AML（ 68 cases） and MDS（ 57 cases） patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. Results： TET2 gene showed the highest mutation rate in AML（ 55. 9 %） and MDS（ 56.1 %）. The gene mutations were as follows： CEBPA（ 11. 8 %）,DNMT3A（ 7. 4 %）,C-KIT（ 7. 4 %） and FLT3-ITD（ 7. 4 %） in AML,and U2 AF1（ 10. 5 %） and SRSF2（ 10. 5 %） in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3,C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack,but the mutation rate of TET2 gene was not obviously changed,whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression,but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. Conclusion： Both AML and MDS have their own specific mutated genes and sites. Some gene mutations,such as CEBPA,can be used as an effective indicator to monitoring MRD in AML patients,but those only used for the evaluation of the disease progression and prognosis in MDS patients.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2017年第6期1631-1635,共5页
Journal of Experimental Hematology
