STUDIES OF P-GLYCOPROTEIN IN CHRONIC MYELOGENOUS LEUKEMIA PATIENTS - EXPRESSION, ACTIVITY AND CORRELATIONS WITH CD34 ANTIGEN

Over-expression of the beta-glycoprotein (Ppg), transmembrane drug eff lux pump, has been shown to cause multidrug resistance of tumour cells (MDR). To investigate the clinical significance of Pgp expression for chronic myeloid leukaemia (CML) diagnosis and monitoring we have stud ied 38 CML patients in various phases of the disease (chronic phase, C P; accelerated phase, AP; blast crisis, BC). Anti-Pgp monoclanal antib ody UIC2 and FACScan analysis were used. Pgp functional activity was i nvestigated by evaluation of verapamil influence upon rhodamine 123 ef flux from the cells. Correlations between Pgp and CD34 expression were investigated. In CP, Pgp-expressing cells were found in 2/14 patients ; in one of them Pgp proved to be non-functional. There were few Pgp-e xpressing cells in AP cases. The group of BC patients consisted of cas es resistant to chemotherapy This gave us the opportunity to consider whether drug resistance of BC CML patients is preferentially connected with Pgp-mediated MDR. 11/22 BC patients had 20% or more of Pgp-expre ssing blasts in the peripheral blood. In all four Pgp(+) BC cases stud ied for Pgp activity this protein was functional. Only 4/ 22 BC patien ts demonstrated large (40% or more) fractions of Pgp(+) blasts. Moreov er, sequential studies of 11 BC CML patients during treatment revealed an increase in the number of Pgp-expressing cells in only two cases. This suggests that Pgp(+) cells did not often accumulate in BC CML, pa tients due to chemotherapy and are the cause of drug resistance in onl y a few cases. A positive correlation between Pgp and CD34 expression was found (r=0.69; P=0.0001). 3/22 BC CML patients had large fractions of both Pgp(+) and CD34(+) blasts in their peripheral blood. The BC C ML patients with this immunophenotgpe of blast cells may represent a s ubtype of BC CML resistant to treatment due to Pgp overexpression.