HIGH MDR1- AND MRP-, BUT LOW TOPOISOMERASE-II ALPHA-GENE EXPRESSION IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIAS

Fifteen samples from 11 patients suffering from chronic lymphocytic leukaemia (CLL; 5 untreated, 6 chemotherapeutically treated) were analysed for their individual gene expression of the multidrug resistance (MDR) associated genes encoding mdrl/P-glycoprotein, mrp, and topoisomerase II alpha/beta-isoenzymes by a complementary DNA polymerase chain reaction (cDNA-PCR) approach. The expression of glyceraldehyde-3-phosphate dehydrogenase (gapdh) served as standard. Thereby, we generally found high mdrl- and mrp-, but low topoisomerase II alpha-mRNA levels. While mdrl levels of the CLL samples were mostly found to be in the range of values measured in the T-lymphoblastoid, P-glycoprotein MDR cell line CCRF VCR 100, mrp levels were usually found to be 2-4-fold higher compared therewith. This might represent a multifactorial MDR in CLL. In contrast to the low or even absent topoisomerase II alpha gene expression, however, the expression of the topoisomerase II beta gene was generally high;in the CU lymphocytes exceeding the value observed in the cell line CCRF VCR 100 up to 5-fold. mdrl gene expression correlated significantly with mrp gene expression in samples from patients having received chemotherapy (r(s) = 0.5833, P < 0.05, n = 10). In two patients the follow-up analysis revealed combined increases in mdrl- and mrp-gene expression levels in the course of the disease.