engleski

ASSESSMENT OF Pgp/MDR1 STATUS IN MULTIPLE MYELOMA BONE MARROW CELLS TREATED WITH CONVENTIONAL AND NEW TREATMENT. MP, VMCP, M2 and VAD/VID versus Velcade and Thalidomide interactions

Multiple myeloma (MM) is an incurable disease of postfolicullar B lymphocytes which enter the bone marrow (BM) and differentiate into myeloma cells. MM is generally considered responsive to chemotherapy ; however, essentially all patients who respond to treatment will relapse and die of drug-resistant disease. As previously shown, MM therapy could induce multidrug resistance (MDR) where the MDR1 gene product membrane transporter P-glycoprotein (Pgp) decreases treatment success through amplified drug efflux. This disease is therefore considered a paradigm for studying the development of acquired MDR. The aim of our study was to elucidate the mechanism of MDR induction in MM patients following different treatments. We followed seventy two consecutive MM patients (34 before therapy) on standard therapy protocols. Treatment implied courses of 4-6 weekly intervals of chemotherapy combinations (MP, VMCP, M2 and VAD), those not eligible for high dose treatment were treated with conventional protocols.The study also included a small group patients treated with modified VID protocol (vincristine, idarubicin, dexamethasone), MDR-independent idarubicin replacing MDR-dependent adriamycin. Due to their efficiency in refractory MM, Thalidomide (Thal) and Velcade&reg ; were introduced in 2006, the first inhibits angiogenesis and the second proteosomes. MDR status (Pgp phenotype and function) was measured with flow cytometry at baseline and on the first day of each cycle on MRK-16+ CD38, CD138 and CD31 BM subsets. The number of MDR+ CD38+/138+ plasma cells increases after MDR-dependent VAD therapy, remains unchanged after M2, VMCP and MP and decreases in the patients on VID protocol. Moreover, only after VID therapy, decreased activity, measured by rhodamine dye efflux, was observed. Our preliminary results in patients with refractory or relapsed MM treated with Thal and Velcade&reg ; indicate the advantage of their combination with Dexamethasone. Probably Thal/Velcade&reg ; /Dex interactions versus VMCP/VAD/VID activate different MDR mechanisms which help overcome chemotherapy resistance and restore sensitivity to MM cells.

Multidrug resistance; multiple myeloma treatment

nije evidentirano