急性早幼粒细胞白血病mdr1、GSTπ表达与耐药的关系

Study of the action of glutathione Mdr1,S-transferase expressionin acute promyelocytic leukemia cell

目的研究多药耐药基因(mdr1)、耐药基因谷胱甘肽S转移酶(GSTπ)在复发难治的急性早幼粒细胞白血病(APL)中的表达及意义。方法实验组:包括敏感组(As2O3治疗APL初治和持续完全缓解的患者)及耐药组(APL用As2O3治疗后复发耐药的患者);对照组:正常人的外周血。均采用荧光定量RT-PCR技术测定GSTπmRNA、mdr1的表达,比较敏感组与耐药组患者GSTπ、mdr1的表达。结果(1)APL患者GSTπ表达:耐药组为70%,敏感组为53.3%,二组阳性表达率无明显差异(P(0.05)。荧光定量分析GSTπ高表达的阳性率,耐药组中的高表达率为60.0%,敏感组中的高表达率为10.0%,耐药组GSTπ高表达率明显高于敏感组(P<0.005)。(2)12例初治患者mdr1全部为阴性表达;耐药组10例mdr1阳性表达为80%。结论As2O3治疗APL后GSTπ高表达与其临床疗效相关,GSTπ的高表达可能为APL耐药的一个指标;而mdr1在APL患者低表达或不表达,耐药组高表达,说明mdr1与As2O3的治疗及预后密切相关。而且荧光定量RT-PCR可能是更为敏感、准确的检测耐药基因GSTπ方法。

Objective： To study the expression and signification of glutathione S- transferase （GSTπ） and mdrl in resistant relaped APL. Mothods ： Experiment group ： sensitive group （the first - tretment patient and the remain complicated - released patients who used As203 ） and chemoresistant group （the resistant relapsed patients who used As203 ）. Control group： healthy persons periphral blood These are detected by fluorescence -quantitative reverse transcription -polymerase chain reaction （RT -PCR） to compare the expression of GSTπ and mdrl between sensitive group and resistant group. Results ： （ 1 ） The expression of GSTπ was 70% in resistant APL and 53.3% in sensitive APL used As203 （ P 〉 0.05 ）, no obvious difference in these groups. Fluorescence - quantitative analysis ： The expression rate （ 60% ） of GSTπ in resistant drug group was significal higher in sensitive drug group （10%） （ P 〈 0. 005）, healthy peasons as well contain low level glutathione S- transferase （GSTπ） gene expression. （2） Mdrl expression in 12 firsttreated patients was all negative, but the positive rate was 80% in 10 drug resistant cases. Conclusion： The hiher expression of GSTπ was related with its clinical application in APL used As203. Mdrl expression was closed related with the therapy and prognosis of As203 in APL. RT - PCR will maybe the more sensitive and accurate method to detece the drug resistant gene.