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MDR1 and MRP expression in chronic B‐cell lymphoproliferative disorders
Author(s) -
Marc Webb,
Marion Brun,
Michelle McNiven,
David G. Le Couteur,
P Craft
Publication year - 1998
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1998.00822.x
Subject(s) - lymphoma , p glycoprotein , medicine , analysis of variance , drug , flow cytometry , lymphoproliferative disorders , drug resistance , immunology , cumulative dose , antibody , gastroenterology , pharmacology , biology , multiple drug resistance , microbiology and biotechnology
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.