Molecular and cellular pharmacologyBortezomib influences the expression of malignant plasma cells membrane antigens

Multiple myeloma cells can be characterized immunophenotypically as the expression levels of several membrane antigens differ from those of normal plasma cells. These antigens are important for making a diagnostic of multiple myeloma; they have a significant role in survival and proliferation of multiple myeloma cells. Analyzing the effect of bortezomib on the expression of surface antigens CD138, CD56, CD27, CD28, CD45 and CD221 and xenograft models, we have found that bortezomib increases the level of CD45 and decreases all other antigens. Bortezomib induces the reduction of IGF-1R (CD221) and syndecan 1 (CD138). This effect was associated with the reduced activation of Ras/MAPK, mTOR/p70S6K and JAK/STAT pathways in response to IGF-1 and IL-6. These results suggest that bortezomib may influence the sensitivity of myeloma cells to soluble growth factors by down-regulation of membrane receptors.