Is multidrug resistance (P-glycoprotein) an intrinsic characteristic of plasma cells in patients with monoclonal gammopathy of undetermined significance, plasmacytoma, multiple myeloma and amyloidosis?

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 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.

• Authors: W Mongkonsritragoon, T Kimlinger, G Ahmann, P R Greipp
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 29 Issue 5-6 Pg. 577-84 (May 1998) ISSN: 1042-8194 [Print] United States
• PMID: 9643571 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Neoplasm Proteins

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (analysis, physiology)
• Adult
• Aged
• Amyloidosis (drug therapy, metabolism, pathology)
• Antineoplastic Agents (therapeutic use)
• Bone Marrow (metabolism, pathology)
• Drug Resistance, Multiple
• Female
• Humans
• Male
• Middle Aged
• Monoclonal Gammopathy of Undetermined Significance (drug therapy, metabolism, pathology)
• Multiple Myeloma (drug therapy, metabolism, pathology)
• Neoplasm Proteins (analysis, physiology)
• Neoplastic Stem Cells (metabolism, pathology)
• Plasma Cells (metabolism, pathology)
• Plasmacytoma (drug therapy, metabolism, pathology)
• Recurrence
• Treatment Failure