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目的:探讨急性白血病患者白血病细胞DNA拓扑异构酶Ⅱ(DNATopoⅡ)活性与多药耐药的关系。方法:采用溴乙锭荧光法对17例初治化疗前及20例化疗后的急性白血病患者外周血或骨髓白血病细胞DNATopoⅡ活性进行测定,采用抗多药耐药单抗JSBⅠ检测18例化疗后患者p糖蛋白表达,采用RTPCR法检测mdr1基因表达。结果:白血病患者化疗前组TopoⅡ活性(0.6415±0.0561)较健康对照组(0.2304±0.0591)显著增高(P<0.005)。化疗后患者白血病细胞TopoⅡ活性(0.3563±0.1011)较化疗前组显著降低(P<0.05)。15例临床疗效差,其中12例p170及mdr1基因表达阳性、3例表达阴性,而TopoⅡ活性均降低。结论:TopoⅡ活性下降可能是患者对抗肿瘤药表现耐药的另一重要原因。
Objective: To investigate the relationship between DNA topoisomerase II (DNA TopoII) activity and multidrug resistance in leukemia cells from patients with acute leukemia. METHODS: DNATopoII activity in peripheral blood or bone marrow leukemia cells was measured in 17 patients with acute leukemia before and after chemotherapy with ethidium bromide fluorescence method. Eighteen patients were treated with anti-multidrug resistant monoclonal antibody JSBI. After the expression of p glycoprotein, the expression of mdr 1 gene was detected by RTPCR. Results: TopoII activity in patients with leukemia before chemotherapy (0.6415±0.0561) was significantly higher than that in healthy controls (0.2304±0.0591) (P<0.005). The TopoII activity (0.3563±0.1011) in patients with leukemia after chemotherapy was significantly lower than that before chemotherapy (P<0.05). In 15 cases, the clinical efficacy was poor, of which 12 cases of p170 and mdr 1 gene expression were positive, 3 cases were negative, and Topo II activity was reduced. Conclusion: The decrease of TopoII activity may be another important reason for the anti-tumor drug resistance of patients.