Patterns of drug resistance parameters in adult leukemia.
P-glycoprotein (Pgp), Glutathione (GSH), Glutathione S-Transferase (GST), and O6-Alkylguanine-DNA Alkyltransferase (ATase) were measured in parallel as putative indicators of drug resistance in adult leukemia. The patterns of resistance parameter expression of chronic and acute leukemia were different. In acute leukemia on average all parameters were increased as compared to normal bone marrow. In chronic leukemia GSH and GST were increased, whereas Atase, GPx and frequency of Pgp-expression were low. Treatment with cytostatic drugs did not influence median levels of expression/activity of the resistance parameters. Resistance parameter expression/activity of leukemic cells was also compared with various other tissue and tumor types. Generally the pattern of resistance parameter expression reflected the resistance status of the tissue, constitutively resistant tumor types and their corresponding normal tissue on average having higher levels than leukemic cells and other tissue and tumor types with acquired resistance. For individual patients with acute leukemia, however, none of the parameters was directly correlated with response to treatment.
Joncourt
F
F
University of Berne, Department for Clinical-Experimental Research, Switzerland.
Oberli-Schrämmli
A E
AE
Stadler
M
M
Buser
K
K
Franscini
L
L
Fey
M F
MF
Cerny
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D008780:Methyltransferases / Q000378:metabolism; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005982:Glutathione Transferase; D005978:Glutathione