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.