AML1-ETO9a异构体在伴t（8；21）M2型急性髓系白血病中表达比例的监测及其意义

Monitoring the expression ratio of AML1-ETO9a isoform in t（8 ;21 ） acute myeloid leukemia and itssignificance

目的 研究AML1-ETO9a （AE9a）异构体在伴有t（8；21）的M2型急性髓系白血病（ AML-M2）患者中表达比例的变化及其临床意义.方法 应用RT-PCR方法筛选了44例初诊AE9a与AML1-ETO（AE）融合基因共表达的伴有t（8;21）的AML-M2患者.应用实时定量PCR技术监测这44例多次随访标本中AE9a在AE9a与AE两者总和中百分比的变化.结果 伴有t（8;21）的44例初诊AML-M2患者中AE表达量高于AE9a（中位CT值分别为20.48和21.54）,两者表达量呈正相关（r =0.900）；44例初诊患者经首次标准方案化疗后AE与AE9a表达量均下降,但初治后AE9a在总体中百分比较初诊时上升（P＜0.05）；患者经1个疗程标准方案化疗后,未达完全缓解（CR）组的AE9a百分比明显高于CR组（中位值分别为36.81％和7.93％,P＜0.05）；复发患者缓解期间AE9a百分比高于未复发患者（中位值分别为22.89％和2.43％,P＜0.05）；缓解期间,17例复发患者中11例AE9a百分比在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,并且AE表达量高于AE9a,两者呈正相关.AE9a异构体对标准化疗的敏感性较AE差.在缓解期监测AE9a在AE及AE9a两者总体中百分比的变化比单独监测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。

Objective To study the expression ratio of AML1-ETO9a （AE9a） isoform in t（8 ;21 ）acute myeloid leukemia （AML） and its clinical significance. Methods Bone marrow samples fi＇om 44 newly diagnosed t（8 ;21 ） AML patients co-expressed AE9a and AE were screened by RT-PCR. The alteration of the AE9a expression ratio was monitored during follow-up by using quantitative real-time RT-PCR（qPCR）. Resuits The expression level of AE9a was markedly lower than that of AE in these patients. There was a positive correlation between the expression level of AE9a and AE in most of bone marrow samples. The transcript level of both AE9a and AE was decreased in the 44 patients after one course of standard chemotherapy, but the percentage of AE9a expression level was increased in comparison with that before treatment （P 〈 0.05 ）. After one course of standard chemotherapy treatment, the percentage of AE9a in incomplete remission （ICR） patients was significantly higher than that in CR patients （ P 〈 0.05）. Relapsed patients had a higher AE9a ratio than the unrelapsed patients （P 〈 0.05 ）. During the remission, the percentage of AE9a in 11/17 relapsed patients obviously elevated even while the expression of AE fusion gene at low level. Conclusions AE9a and AE co-expressed in most of AML patients with t（ 8 ;21 ） translocation. The expression level of AE9a was lower than that of AE, and there is a positive correlation between the expression level of these two isoforms. The sensitivity of AE9a gene to the standard chemotherapy is less than that of the AE fusion gene. Monitoring the AE9a to AE ratio during the CR can predict the early relapse of the disease compared to monitoring the AE alone.