engleski

Relevance of Pgp expression and activity in multiple myeloma patients treated with Idarubicin based chemotherapy

Multiple myeloma (MM) is still incurable because the malignant clone resists complete eradication following the treatment. The reason for chemotherapy failure has been associated with the development of multidrug resistance (MDR) and the need for MDR-independent regimens has emerged. In this sense, VID protocol (vincristine, idarubicin, dexamethasone) has been created, using MDR-independent idarubicin instead of the MDR-dependent adriamycin to overcome the effect of the MDR1 gene product P-glycoprotein (Pgp). The purpose of this follow up study was to asses Pgp phenotype and function in bone marrow (BM) cells of MM patients treated according to standard MM chemotherapy protocols, including VID. The Pgp phenotype of BM plasma cells was analyzed using the CD38/CD138/MRK-16 combination and Pgp activity was measured in the rhodamine dye functional efflux assay. Pgp expression on CD38+ cells increased with the advanced clinical stage of the disease, with the strongest Pgp expression in stage III (pI, III<0.01). Pgp expression on CD38/CD138 population increased after both MDR-dependent treatment and VID, but was significantly lower following VID treatment (p<0.01 compared to VAD-treated MM). High percentage of Pgp+ plasmocytes was observed in MM not responding to therapy (p<0.01) and in those with fatal outcome (p<0.05). Furthermore, the BM cells of patients receiving idarubicin-based chemotherapy had lower Pgp activity than VAD or untreated patients. At the clinical level, this indicates that idarubicin may have the ability to suspend Pgp activity thus increasing the intracellular drug concentration. Idarubicin seems to circumvent MDR, however, further studies are needed to evaluate its chemotherapeutic efficacy in the treatment of MM.

Pgp; Multiple myeloma; Idarubicin

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