Cytostatic drug resistance: parallel assessment of glutathione‐based detoxifying enzymes, O6‐alkylguanine‐DNA‐alkyltransferase and P‐glycoprotein in adult patients with leukaemia

Publisher Website
Google Scholar
Abstract
Summary. The levels of several potential indicators of resistance to cytostatic drugs were measured in leukaemic cells of a total of 64 adult patients with acute or chronic Ieukaemias before and during treatment and at relapse or recurrence of disease and compared with those of mono‐nuclear cells from the bone marrow of healthy donors. The resistance factors included glutathione (GSH) and its associated enzymes glutathione‐S‐transferase (GST) and glutathione peroxidase (GPx) as well as O6‐alkyguanine‐DNA‐alkyltransferase (ATase) and P‐glycoprotein. Median values for most parameters were significantly higher in leukaemic cells than in those of normal donors although wide interindividual variation in the values of the various parameters, particularly GST, were seen. P‐glycoprotein was measurable in 12.5% of untreated leukaemias but in none of the normal donors. The values of the parameters in untreated leukaemic patients were not statistically different from those at relapse or during disease progression. However, the median values for GSH, GST and GPx but not ATase in samples from untreated patients were significantly higher than those in samples taken during drug treatment. Patient response, disease‐free survival or duration of remission did not correlate with the values of any of the parameters studied.

This publication has 28 references indexed in Scilit: