Differential expression of Bcl-2 in human plasma cell disorders according to proliferation status and malignancy

Multiple myeloma (MM) is a malignancy characterized by a very slow prolifer ation of malignant plasma cells leading to their accumulation within the bo ne marrow. This suggests that resistance to apoptosis may play a critical r ole both in the pathogenesis and resistance to treatment of MM. Bcl-2 is a key protein for the regulation of apoptosis. However, it has been shown tha t this protein also regulates the state of proliferation. In the current st udy, we show that malignant plasma cells from both the bone marrow and peri pheral blood express high levels of Bcl-2 and are slowly proliferating cell s. In contrast, myeloma cells from extramedullary sites (ie pleural effusio n, ascitis, mammary and gastric plasmacytoma) express Bcl-2 weakly while be ing highly proliferative. Normal non-dividing bone marrow plasma cells expr ess high levels of Bcl-2 protein. In contrast, four highly proliferative re active plasmacytosis express weak levels of Bcl-2. We conclude that there i s an inverse correlation between Bcl-2 expression and the proliferation rat e of both normal and malignant plasma cells. These data may be explained by the double function of Bcl-2, ie its well known function as an anti-apopto tic molecule and its intriguing function as an inhibitory molecule of cell proliferation.