白血病细胞内谷胱甘肽硫转移酶的表达与化疗耐药的关系

The Expression of Glutathione S-Transferase in Leukemic Cells and Resistance to Chemotherapy

为了探讨白血病细胞内谷胱甘肽硫转移酶 (GST)的表达与化疗耐药的关系 ,本研究采用 1 氯 2 ,4 二甲基为底物的比色分析法和原位杂交法对 5 6例白血病患者白血病细胞内GST的表达进行检测 ,并结合临床化疗药物敏感度和治疗效果进行临床分析。结果显示 :①同类型白血病患者的白血病细胞内GST表达 ,无显著性差异 ;②初治和复发白血病患者白血病细胞内GST活性分别为 (4.5± 1.0 )U和 (7.9± 1.5 )U ,GSTmRNA表达率分别为33.3%和 6 6 .3% ;③ 5 6例白血病患者在临床完全缓解 (CR ,19例 )、部分缓解 (PR ,2 0例 )和未缓解 (NR ,17例 )组的GST活性分别为 (1.7± 0 .7)U ,(5 .9± 2 .0 )U和 (9.3± 1.7)U ,GSTmRNA表达率分别为 13.3% ,2 9.7%和76 .6 %。结论提示 :白血病细胞内GST异常表达与白血病化疗耐药明显相关 ,高表达GST的患者易复发 。

In order to study the relationship between the expression of glutathione S transferase(GST) in leukemic cells and the chemoresistance in patients with acute leukemia, the expressions of GST activity and GST mRNA were measured according to spectrophotometric assay based on the use of 1 choloro 2, 4 dinitro benzene and in situ hybridization. The results were studied in corelation with some clinical and pathological data. Results showed that: 1. There is no significant differences between activities of the enzyme with the different leukemia types according to the FAB classification. 2. GST activity and GST mRNA expression in the patients, both untreated and relapse, were (4.5±1.0) U, 33.3% and (7.9±15) U, 66.3% respectively. 3. In 56 patiemts, GST activity was 1.7±0.7, 5.9±2.0 and 9.3±1.7 U and GST mRNA expression was 13.3%, 29.7% and 76.6%, respectively, in CR, PR and NR groups. The lowest values of GST activity and GST mRNA expression were observed in those patients who achieved complete remission. The highest values of GST activity and GST mRNA expression were observed in those patients with no response to treatment. It was concluded that the expression of GST in patients with acute leukemia is closely related to the chemosensitivities clinically. Determinations of GST activity and GST mRNA are useful for predicting the chemosensitivities and the prognosis of the disease.