LEVELS OF MDR1 AND MRP MESSENGER-RNA IN LEUKEMIC-CELL POPULATIONS FROM PATIENTS WITH ACUTE MYELOCYTIC-LEUKEMIA ARE HETEROGENOUS AND INVERSELY CORRELATED TO CELLULAR DAUNORUBICIN ACCUMULATION

Multidrug resistance gene (mdr1) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML), Whether expression of t he recently described multidrug resistance-associated gene (mrp) has a ny prognostic importance in AML is still unclear. The aim of the prese nt study was to investigate the functional role of the mdr1 and mrp mR NA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubat ed with daunorubicin (DNR). Cellular DNR content was analysed with a f luorescence-activated cell sorter (FAGS). From each cell population th e 20-25% cells with the lowest and highest DNR content were sorted out , and mdr1 and mrp RNA were quantified in these subpopulations with co mpetitive polymerase chain reaction. The ratio between the mean DNR co ntent in the cell populations with high and low DNR content varied bet ween 1.9 and 6.6. The cell fraction with low DNR content had higher (3 .8-40 times) mdr1 mRNA levels in 10/10 patients and higher (1.4-26 tim es) mrp mRNA levels in 8/10, as compared to the cell fraction with hig h DNR accumulation. In conclusion, mdr1 and mrp mRNA expressions are h eterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely corre lated to DNR accumulation in vitro.