engleski

Impact of multidrug resistance-associated Pgp and CD38 phenotype on treatment response in B-CLL

The aim of this study was to find out if P-glycoprotein (Pgp), a marker of multidrug resistance (MDR), and CD38 molecule, a marker of activated and/or plasma cells , are an intrinsic feature of normal and/or leukemic lymphocytes and how their expression influences chemotherapy. Study population cosisted of 42 B-CLL patients and 36 healthy volunteers. Pgp was detected with C-219 and MRK-16 anti Pgp monoclonal antibodies (mAbs) and analysed by flow cytometer. In the group of healthy volunteers, the percentage of Pgp-positive cells progressively increased with age. Comparison with the age-matched group of healthy volunteeers showed significantly higher percentage of Pgp in the groiup of CLL patients. Pgp level was calculated as a ratio of mean fluorescence (Pgp specific/isotypic control, RMF) where RMF>1, 5 is considered as positive. Chemotherapy decreased Pgp expression, RMF values for both epitopes were significantly decreased irrespectively of the clinical status. In a separately monitored group of 13 patients, before and after treatnent with MDR-independent drugs (Chlorambucil or purine analogs) those who entered complete and partial remission had decreased RMF values for both Pgp epitopes, opposing unchanged or even increased RMF values in those who did not respond to therapy. Our data indicate that levels of Pgp expression and their dynamics correlate with the clinical response to therapy, even when the Pgp mechanism non-dependent drugs are used. In addition, using CD38 and CD34 mAbs we analysed clinical relevance of CD38 molecule in B-CLL. Only part of them (5/14) were CD38 positive, predominantly CD34- patients with mild (RAII) clinical course, whereas lower CD38 lymphocyte profile was associated with a more aggressive (RAI2 &3 and CD34+) form of the disease. According to the observations in our study, related to the Pgp and CD38 expression, and because effective chemotherapy downregulates Pgp and upregulates CD38 profile, we suggest biological significance and importance of Pgp and CD38 monitoring in B-CLL patients.

MDR; Pgp phenotype; CD38; B-CLL

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