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

The expression of glutathione transferase π (GSTπ) 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 GSTπ coupled with peroxidase antiperoxidase staining was used for immunodetection of GSTπ 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 GSTπ 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 GSTπ (P ≤ 0.03). Of 40 sections that showed a low expression of GSTπ, 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 GSTπ 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 GSTπ. The expression of GSTπ remained rather constant in most patients as the disease progressed to clinical resistance. At relapse there was no significant correlation between the expression of GSTπ 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 GSTπ at the time of diagnosis and the subsequent treatment results and that GSTπ is a useful marker for clinical resistance to cytostatic drugs in acute nonlymphoblastic leukemia.