急性白血病患者白血病细胞DNA拓扑异构酶Ⅱ活性与多药耐药的研究

Study on the relationship between DNA topoisomerase Ⅱ activity and multidrug resistance in leukemic cells

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ＪＳＢⅠ检测１８例化疗后患者ｐ糖蛋白表达，采用ＲＴＰＣＲ法检测ｍｄｒ１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ｍｄｒ１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 explore the relationship between DNA topoisomerase Ⅱ (Topo Ⅱ) activity and multidrug resistance in acute leukemia(AL). Methods: Topo Ⅱ activities were measured in peripheral blood or bone marrow leukemia cells from 17 pretreated patients and 20 after combination chemotherapy by fluorometric assay. In the same time, multidrug resistant p glycoprotein expression was detected by immunohistochemistry using JSB 1 monoclonal antibody and mdr 1 gene expression was assayed by RT PCR in 18 post chemotherapy patients. Results: Topo Ⅱ activities were significantly higher in pretreated AL patients (0.6415±0.0561) than in healthy blood donors (0.2304±0.0591)(P<0.005) and significantly lower in post chemotherapy patients (0.3563±0.1011) than in pretreated ones (P<0.005). Among 15 poorly responsed patients, 12 were p170 positive and mdr 1 overexpression, 3 case were p170 negative. Topo Ⅱ activity was also decreased in these poor responsers. Conclusion: Decreased Topo Ⅱ activity may be another factor in multidrug resistance.