Is Multidrug Resistance (P-Glycoprotein) an Intrinsic Characteristic of Plasma Cells in Patients with Plasma Cell Dysclasia?
Keywords:
P-glycoprotein, Multidrug resistance (MDR), Monoclonal gammopathy, Multiple myeloma, AmyloidosisAbstract
Abstract : Multiple myeloma is not a curable disease, and most patients relapse after plateau phase. Drug resistance is a major problem in effective chemotherapy in this kind of disease. Current approaches are aimed at reversing or preventing drug resistance late in the disease. We studied a drug resistance marker, P-glycoprotein (P-gp), in a total of 43 patients with monoclonal gammopathy. This group included eight with monoclonal gammopathy of undetermined significance (MGUS), five with plasmacytoma (PCM), nineteen with multiple myeloma (MM; six newly diagnosed, seven plateau, five reffactory, one relapse) and eleven amyloidosis (seven newly diagnosed, four after treatment). Using 3-color flow cytometry, a plasma cell gate was selected on the basis of CD38+/45-(dim) staining and the population was examined for the expression of P-gp using two monoclonal antibodies (MRK16 and UIC2) P-gp expression was positive on marrow plasma cells in 42/43 patients. The resistance index (Rl) in these cases (range 2.0-7.07) is comparable to that in the positive cell line KG-1A (3.05-3.08). These data suggest that relative resistance due to the P-gp mechanism is likely to be an intrinsic property of plasma cells in monoclonal gammopathies and may provide a partial explanation as to why these diseases always relapse. Strategies for MDR reversal need to be considered earlier in the course.
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