Significant expression of MDR-1 mRNA and P-glycoprotein was not detected in 25 cases of multiple myeloma prior to chemotherapy and even after several courses of VAD (vincristine, adriamycin and dexamethasone) therapy by Northern blotting and immunostaining using monoclonal anti-P-glycoprotein antibody (MRK-16), respectively.
MDR1 has been the most studied in hematological malignancies, particularly in lymphoma and multiple myeloma (MM), diseases generally considered as overexpressing such mechanisms in relapse.
Studies of acute myelogenous leukemia, lymphoma, and myeloma in adults have so far provided the best evidence for a relevant role for P-glycoprotein as a cause of clinical multidrug resistance.
Although expression of the Mr 170,000 P-glycoprotein drug pump is likely to play a role in multidrug resistance (MDR) in haematological malignancies, it is now evident that other MDR mechanisms may be operational as well in leukaemias, lymphomas, and multiple myeloma.
Studies in myelogenous leukemia and myeloma have so far provided best evidence for a significant correlation between P-glycoprotein expression and response to chemotherapy, although large discrepancies in the proportion of positive cells limit any definite conclusion.
Clinical studies in patients with myeloma have shown that some patients with P-gp-positive cancer cells respond to the chemosensitizing effect of verapamil.
Recently, clinical reversal of MDR by noncytotoxic P-gp modulators such as verapamil, cyclosporin A (CsA), and PSC 833 was explored in acute leukemia and multiple myeloma.
Nevertheless, a careful analysis of the literature on MDR1 expression in multiple myeloma (MM) shows the existence of disturbing discrepancies as regards both the incidence of MDR1 over-expression and its clinical value.
This study evaluated the prognostic role of MDR1 in the outcome of 115 multiple myeloma patients treated with DAV (dexamethasone, doxorubicin [adryamicin] and vincristine) regimen followed by autologous transplantation.
These results support the hypothesis that genetic variability of MDR1 should be considered as an important factor that influences the clinical outcome of multiple myeloma.
These results support the hypothesis that genetic variability of MDR1 should be considered as an important factor that influences the clinical outcome of multiple myeloma.
Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin.