Is multidrug resistance (P-glycoprotein) an intrinsic characteristic of plasma cells in patients with monoclonal gammopathy of undetermined significance, plasmacytoma, multiple myeloma and amyloidosis?
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 refractory, 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 (RI) in these cases (range 2.0-7.07) is comparable to that in the positive cell line KG-1A (3.05-3.08). In 2 of 5 patients with refractory MM, the RI for P-gp (5.4, 6.36) was higher than in plateau phase. 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. The results of our study support strategies for MDR reversal earlier in the course.
Mongkonsritragoon
W
W
Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Kimlinger
T
T
Ahmann
G
G
Greipp
P R
PR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000502:physiology; D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D010954:Plasmacytoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D012008:Recurrence; D017211:Treatment Failure
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins