CLINICAL IMPLICATION OF P-GLYCOPROTEIN, M ULTIPLE-DRUG RESISTANCE PROTEIN, EXPRESSION IN CHRONIC MYELOID-LEUKEMIA (CML)

Cell resistance to pharmaceutical agents arises among other causes bec ause of multiple drug resistance induced by P-glycoprotein (P-gp). The analysis of expression of P-gp and differentiation antigens of hemopo ietic cells has been made on myeloid cells from 14 patients in CML chr onic phase and 25 with CML acceleration and in blast crisis. Surface a ntigen expression was evaluated at flow cytofluorimetry (FACScan u nit ). Fluorescent dye rodomin (Rh123) helped examine P-gp functional acti vity. A close relationship is shown between P-gp expression and CD34 ( r = 0.69. p = 0.0004), this giving evidence of these antigens expressi on on the same cells. In chronic phase P-gp is expressed on a few cell s in some patients, its activity being low or absent. The appearance o f UIC-2(+) cells was unrelated to previous chemotherapy and brought no resistance to treatment. In terminal stage P-gp is expressed in 50% o f cases. Functional tests identified the active protein in blast popul ations with a large number of UIC-2(+) cells and in some patients with a small number of cells expressing P-gp. Therefore, comprehensive cli nical investigations are needed of multiple drug resistance, though in half of the resistant patients in AML blast crisis P-gp(+) cells were not identified suggesting the existence of other mechanisms responsib le for resistance to treatment.