The significant role for the loss of CD27-expression in myelomagenesis

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CD27 is a marker of memory B cells, and its interaction with its ligand, CD70, is very important for the differentiation into plasma cells. Although CD27 is detected on normal plasma cells, the expression of CD27 is significantly reduced with the progression of multiple myeloma (MM) including monoclonal gammopathy of undetermined significance (MGUS). CD27^+ myeloma cells are thought to represent on early phase of myeloma, since CD27^+ plasma cells from patients with MM were found to be composed of normal plasma cells (CD 19^+/CD38^<++>) and myeloma cells (CD 19^-/CD38^<++>), and monoclonality was detected in the CD27^+/CD38^<++> fraction. Given that the lack of CD27 on plasma cells is related to myelomagenesis and that the proapoptotic protein Siva is thought to bind to the cytoplasmic tail of CD27, we analyzed alterations of cell growth and genes caused by co-culturing CD27-transfected myeloma cell lines (U266, KMS-5) with CD70-transfected NIH3T3 cells. CD27-CD70 interaction could not induce apoptosis in either type of myeloma transfectant, and binding between Siva and CD2? was not detected. cDNA microarray (Human Apoptosis CHIP) analysis showed significant up-regulation of expression of the ectodermal neural cortex 1 (ENC 1) gene by CD27-CD70 interaction compared with CD27 transfection alone. These findings show that the relationship between the loss of CD27 and oncogenesis of plasma cells is not simple. It remains unclear whether the lack of CD27 leads to evasion of apoptosis