The relevance of multidrug resistance-associated P-glycoprotein expressionin the treatment response of B-cell chronic lymphocytic leukemia

Background and Objectives. The aim of this study was to determine whether e xpression of P-glycoprotein (Pgp) is an intrinsic feature of B-lymphocytes in B-cell chronic lymphocytic leukemia (B-CLL) and how it correlates with h ematologic indices and tumor load in the disease. Furthermore. the change o f Pgp expression under cytotoxic treatment and its correlation to treatment outcome were studied, Design and Methods. In 42 B-CU patients, of whom 13 were sequentially monit ored, expression of extracellular (MRK-16) and intracellular (C-219) Pgp ep itopes on peripheral blood lymphocytes was determined by now cytometry anal ysis and quantified by ratio of the mean fluorescence (RMF) in flow cytomet ry analysis. Results. Median RMF values in B-CLL patients were higher than In age-matche d controls. Pgp expression did not correlate with any of the hematologic fe atures or clinical stage of the disease, patients who received some type of cytoreductive treatment prior to the study had lower Pgp values for both m easured epitopes (median RMF for C-219 and MRK-16 of 1.99 and 2.03 in compa rison to those of nontreated patients: 3.11 and 2.88, respectively). In 13 patients monitored during treatment the decrease in RMF was noted after tre atment with chlorambucil, with RMF values for both Pgp epitopes decreasing in responders, This was In contrast to unchanged or even Increased RMF valu es in those patients who did not respond to therapy. interpretation and Conclusions. Our study confirms the importance of quanti tative evaluation of Pgp expression by flow cytometry. At the clinical leve l, cross-sectional, single test evaluation of Pgp is of limited value where as sequential follow-up values correlate with treatment response. (C) 2000, Ferrata Storti Foundation.