GLUTATHIONE SYSTEM, TOPOISOMERASE-II LEVEL AND MULTIDRUG-RESISTANCE PHENOTYPE IN ACUTE MYELOGENOUS LEUKEMIA BEFORE TREATMENT AND AT RELAPSE

In order to better understand acquired resistance to antitumor agents in acute myelogenous leukemia (AML) we investigated various drug resis tance mechanisms; namely topoisomerase II (topo II), glutathione syste m and P-glycoprotein (P-gp). Blast cells of 31 patients with AML, 21 b efore treatment (BT) and 10 at relapse (AR) were studied Topo II was e valuated by Western blot analysis. Glutathione-S-transferase activity (GST) and glutathione content (GSH) were investigated by spectrophotom etric assays. GST isoenzymes (-alpha, -mu and -pi) were tested by West ern blot and by immunocytochemical staining. P-gp was evaluated by an immunocytochemical method using MRK 16 antibody. Our results showed th at GST, GSH and GST-pi were similar in patients BT and AR. GST-mu was detected in 13/21 AML BT and in 5/10 AML AR. GST-alpha expression was higher (p < 0.05) in AML AR (60 +/- 105 AU/mg) compared to AML BT (10 +/- 10 AU/mg). A relationship was found between GST-pi quantitation ev aluated by Western blot and immunocytochemical staining, whereas no co rrelation was observed for the other isoenzymes. Topo II was detected in only 4 AML BT and 3 AML AR. Eleven out of 21 AML BT and 3/10 AML AR expressed P-gp with immunohistochemical study. These results indicate that only the ''glutathione system'', especially the GST-alpha could be involved in drug resistance in AML.