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Expression of Glutathione Transferase as a Predictor for Treatment Results at Different Stages of Acute Nonlymphoblastic Leukemia¹

Division of Clinical Hematology and Oncology, Department of Medicine [U. T., C. P.] and Department of Pathology [A. E-R., L. C. E.], Huddinge Hospital and Karolinska Institutet, S-141 86 Huddinge, and Department of Biochemistry [X-Y. H., B. M.], Uppsala University, Biomedical Center, Box 576, S-751 23 Uppsala, Sweden

The expression of glutathione transferase (GST) was studied in leukemic cells from 60 patients with acute nonlymphoblastic leukemia at diagnosis and at progressing stages of the disease. A polyclonal rabbit antibody to human placental GST coupled with peroxidase antiperoxidase staining was used for immunodetection of GST on sections of routinely fixed bone marrow clots. All patients had received induction therapy based on an anthracycline and a standard dose of ara-C. The expression of GST at diagnosis was significantly correlated with response to induction therapy, duration of first remission, and overall survival. Twenty-nine of 36 samples of bone marrow from patients that entered complete remission (CR) following primary induction therapy showed a low expression, whereas nine of 16 sections from patients with resistant disease showed a high expression of GST (P 0.03). Of 40 sections that showed a low expression of GST, 29 (73%) were taken from patients that achieved a CR, whereas 12 of 19 sections that showed a high expression of the enzyme were from patients with resistant disease or that entered CR only after additional therapy (P 0.02). The median duration of first CR was 18.2 mo for patients whose cells showed a low expression of GST compared with 6.7 mo for those that entered CR in spite of a high expression of the enzyme (P 0.005). Of cells from ten patients that at the time of study were in a continuous first CR, none expressed high concentrations of GST. The expression of GST remained rather constant in most patients as the disease progressed to clinical resistance. At relapse there was no significant correlation between the expression of GST and treatment results but, of ten patients that entered a second CR or achieved a partial remission, only one showed a high expression of the enzyme. We conclude that there was a significant correlation between the expression of GST at the time of diagnosis and the subsequent treatment results and that GST is a useful marker for clinical resistance to cytostatic drugs in acute nonlymphoblastic leukemia.

¹ This study was supported by grants from the Swedish Medical Research Council, the King Gustav the Fifth Jubilee fund, the Swedish Fund for Research without Animal Experiments, and the Swedish Cancer Society.

² To whom requests for reprints should be addressed.

Received 6/21/91. Accepted 4/ 3/92.

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