Effects of Interferon Alpha on Myeloma Cells: Mechanisms of Differential Responsiveness

Abstract

Multiple myeloma is a progressive and fatal disease characterized by the accumulation of malignant plasma cells in the bone marrow. We have been interested in understanding the mechanisms of growth control in myeloma cells. By way of introduction, Figure 1 is a schematic depiction of the proposed progression from monoclonal gammopathy of undetermined significance (MGUS) into myeloma. The incidence of MGUS over the age of 60 has been shown to be approximately 1% and incidence increases to 3% in individuals over the age of 70 (reviewed in 1). Importantly, it has been shown that a significant proportion of MGUS patients will progress into myeloma over time (2). The key distinguishing features between MGUS and myeloma include the absence of lytic bone lesions (MGUS; 3) and differences in the proliferative index of the monoclonal plasma cell population. Thus, a well-documented change that occurs during the progression from MGUS to myeloma is an increase in the plasma cell labeling (proliferative index) of the plasma cell (LI; 4, 5). Because of the key differences between the growth properties displayed by benign (MGUS) and malignant (myeloma) plasma cells, we have had a keen interest in understanding the mechanisms of growth control. Figure 1 suggests that key changes that may occur during this progression include alterations in cytokine responsiveness, acquisition of autocrine growth factor expression, or alterations in cytokine receptor expression.