engleski

Multidrug resistance-associated P-glycoprotein phenotype impact on treatment response in B-CLL

Objective: The relevance of P-glycoprotein (Pgp), a marker of multidrug resistance (MDR) in B-CLL is controversial. The aim of our study was to investigate whether the MDR status at diagnosis correlates with the clinical data (modified Rai, total tumour mass (TM), total lymphocyte count (TLC) and therapy outcome. Design and Methods: Study population consisted of 42 patients (25 males, 17 females with a mean age 62±12 yrs). Expression of Pgp was analyzed on flow cytometer using two mAbs against intracellular (C-219) and extracellular (MRK-16) Pgp epitope. As, due to low Pgp expression, percent of Pgp+ cells is not an adequate value, therefore Pgp level was calculated as a ratio of mean fluorescence (Pgp specific/isotypic control, RMF) where RMF>1, 5 is considered as positive. Results: in 31 non-treated B-CLL patients elevated RMF (median C-219=3, 11 and MRK-16=2, 88) was found, with no correlation to TLC, TTM or modified Rai. We monitored patients who underwent chemotherapy with MDR-independent drugs (chlorambucil or purine analogs). Patients responding to therapy (complete or partial remission) had significant decrease of both C-219 and MRK-16 Pgp-RMFs (medians 6, 78 to 2, 43 and 3, 0 to 1, 35, respectively). The non-responders had unchanged or increased Pgp-RMF. Conclusions: Our data indicate the importance of MDR monitoring in an attempt to treat resistant B-CLL patients with MDR-related drugs.

MDR; B-CLL; Pgp phenotype

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