MDR1 and MRP expression in chronic B-cell lymphoproliferative disorders.
The role of the MDR1 and MRP genes in drug resistance in patients with chronic lymphocytic leukaemia (CLL)/non-Hodgkin's lymphoma (NHL) is unclear. We hypothesized that any relationship between levels of expression and exposure to P-glycoprotein (P-gp) transportable drugs may become evident by using a measure of gene expression that combined the number of positive cells and the degree of positivity. 68 CLL/NHL patients were analysed using flow cytometry with MDR1 and MRP specific antibodies and were divided into subgroups, untreated (n = 31). treated with non P-gp transportable drugs (n = 26), those treated with low total doses of P-gp transportable drugs (n = 6) and patients treated with high total doses of P-gp transportable drugs (n = 5). The group exposed to high doses of P-gp transportable drugs had higher levels of MDR1 expression when compared to all other groups (P<0.05, ANOVA). A positive correlation between the level of MDR1 expression and the cumulative dose of P-gp transportable drugs was demonstrated (P=0.02). MRP expression was higher in those patients exposed to high doses of P-gp transportable drugs when compared to all other groups (P<0.05. ANOVA), although only a trend towards a linear dose correlation effect could be established (P=0.08). We concluded that MDR1 and MRP are involved in drug resistance but only in patients treated with P-gp transportable drugs.
Webb
M
M
Canberra Clinical School, University of Sydney, The Canberra Hospital, Australia.
Brun
M
M
McNiven
M
M
Le Couteur
D
D
Craft
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins