Cytostatic drug resistance: parallel assessment of glutathione-based detoxifying enzymes, O6-alkylguanine-DNA-alkyltransferase and P-glycoprotein in adult patients with leukaemia.
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 leukaemias before and during treatment and at relapse or recurrence of disease and compared with those of mononuclear 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.
Joncourt
F
F
University of Berne, Department for Clinical-Experimental Research, Switzerland.
Oberli
A
A
Redmond
S M
SM
Fey
M F
MF
Tobler
A
A
Margison
G P
GP
Gratwohl
A
A
Buser
K
K
Cerny
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D019853:O(6)-Methylguanine-DNA Methyltransferase
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D005979:Glutathione Peroxidase; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005982:Glutathione Transferase; D005978:Glutathione