Flow cytometric analysis of glutathione-S-transferase-pi in acute leukemia

Abstract

Increased expression of glutathione-S-transferase isoenzyme pi (GST-pi) may account for drug resistance and treatment failure in hematologic malignancies when alkylating agents like cyclophosphamide, chlorambucil, busulfan and melphalan, or doxorubicin are used. We have studied the expression of GST-pi in peripheral blood lymphocytes of healthy blood donors. In peripheral and bone marrow lymphocytes/blasts of patients with other diseases than hematologic malignancies, and of patients with acute leukemia by using flow cytometry. We studied bone marrow cells of 35 patients diagnosed as having acute leukemia at initial presentation, 16 patients in the refractory stage, 20 in morphological remission and 15 controls. None of the samples obtained in remission contained more GST-pi-positive cells than the controls, whereas 51% of the samples obtained at diagnosis and 56% of those obtained in the refractory stage were GST-pi-positive. The mean proportion of GST-pi-positive cells in the lymphocyte/blast cell gate of bone marrow cells of controls was 2.6% and of patients with acute leukemia studied at diagnosis 16.6%, respectively. We analyzed the samples also for P-glycoprotein expression. There was a significant positive association between GST-pi and P-glycoprotein expression in acute leukemia.