联合检测AML1-ETO及其9a异构体在微小残留白血病监测中的意义  

The significance of monitoring minimal residual disease by joint detecting the AML1-ETO and 9a isomer

作　　者：何飞[1] 潘晓芬[1] 陈永昌 梁昌达[1] 易丽君 李红 HE Fei;PAN Xiaofen;CHENG Yongchang;LIANG Changda;YU Lijun;LI Hong(Jiangxi Provincial Children's Hospital,Nanchang Jiangxi,330006)

机构地区：[1]江西省儿童医院,江西南昌330000 [2]江西省全南县人民医院,江西全南341800 [3]江西省儿科研究所中心实验室,江西南昌330000

出　　处：《实验与检验医学》2018年第6期824-828,共5页Experimental and Laboratory Medicine

基　　金：江西省卫计委科技计划(20151135)

摘　　要：目的研究AMLl-ET0及其9a异构体在急性髓系白血病M2型中治疗前后及复发时的表达水平的变化,探讨其对微小残留白血病监测的意义。方法选择2010年1月至2014年1月46例急性髓系白血病患者为研究对象,均经联合化疗获得完全缓解,骨髓采集时间在初诊时、诱导化疗结束时、随访每6个月检测1次以及复发时,随访时间为3年。利用RQPCR方法监测AML1-ETO及9a异构体融合基因的表达水平,总结分析两者的表达水平与临床参数之间的相关性。结果在46例确诊伴有t (8;21)的AML-M2患者的骨髓标本中有41例检测到AE9a异构体,占89.13%。21例复发患者均检测到AE9a异构体;41例AE及AE9a均阳性患者,21例复发,20例未复发,复发组平均表达水平高于未复发组,并且两组对比,AE9a比AE高的更明显(P<0.01);经化疗获完全缓解后,AE、AE9a表达水平均下降,但复发组下降的百分比低于未复发组,差异有统计学意义(P<0.05);比较复发组AE、AE9a化疗前后的变化发现,AE下降的水平明显高于AE9a (P<0.01);缓解期间,21例复发患者中14例AE9a在AE表达低水平时即出现升高甚至异常升高。结论 AE9a与AE共表达于伴有t (8;21)的AML-M2患者中,AE9a异构体对标准化疗的敏感性较AE差。作为微小残留白血病的监测,同时检测AE及AE9a两者表达水平的变化比单独检测AE融合基因能更早地预示疾病复发趋势,从而可提前进行临床干预,降低患者的复发率,提高患者的长期生存率。Objective To quantify the expression levels of AMLl-ETO fusion gene(AE)and AMLl-ETO9a isoform(AE9a)in patients with acute myeloid leukemia(AML)and their possible clinical significance for monitoring minimal residual disease(MRD).Methods A total of 46 cases of acute myeloid leukemia patients were included in the study,All of them achieved complete remission after combined chemotherapy.Bone marrow was collected at the time of initial diagnosis,at the end of induction chemotherapy and at the time of relapse,respectively.The follow-up time was 3 years,during which the bone marrow was detected once every 6 months.The expression levels of AML1-ETO and 9a isomers were monitored using RT-PCR method,and the correlation between the expression level and the clinical parameters was summarized.Results The 46 patients diagnosed the AML-M2 patient with t(8;21),the AE9a isomers were detected in 41 cases,accounting for 89.13%;AE9a isomers were detected in all 21 relapsing cases;Out of 41 cases of AE and AE9a positive cases,21 cases relapsed,20 cases unrelapsed,and the average expression level of the relapsing group was higher than that of the unrelapsed group,and the AE9a was higher than AE(P<0.01);The expression levels of AE and AE9a decreased after complete response,but the percentage of relapse group decreased less than the unrelapsed group,and the difference was statistically significant(P<0.05);AE decreased significantly higher than AE9a(P<0.01)after chemotherapy.During the remission,14 out of 21 relapsed patients showed elevated or even abnormal AE9a expression at low levels of AE.Conclusions AE9a and AE were coexpressed in AML-M2 patients with t(8/21).The sensitivity of AE9a isomers to standard chemotherapy was lower than that of AE.As a monitoring of minimal residual leukemia,detection of the expression level of AE and AE9a at the same time can predict the trend of disease recurrence earlier than the detection of AE fusion gene alone,so that the clinical intervention can be carried out in advance and the recurrence rate o

关 键 词：急性髓系白血病 融合基因 AMLl-ETO 异构体 逆转录聚合酶链反应 微小残留白血病 

分 类 号：R557[医药卫生—血液循环系统疾病] R446[医药卫生—内科学]