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

CD27是记忆B细胞的标志物，其与其配体CD70的相互作用对其向浆细胞的分化具有重要意义。虽然CD27在正常浆细胞上表达，但随着多发性骨髓瘤(MM)的进展，CD27的表达显著减少，包括意义不明的单克隆性伽马病(MGUS)。多发性骨髓瘤患者的CD27^+浆细胞由正常浆细胞(CD19^+/CD38^&t；++&gt；)和骨髓瘤细胞(CD19^-/CD38^&lt；++&gt；)组成，CD27^+/CD38^&lt；++&gt；鉴于浆细胞上CD27的缺失与骨髓瘤的发生有关，以及促凋亡蛋白SIVA被认为与CD27的胞浆尾部结合，我们分析了CD27转基因的骨髓瘤细胞株(U266，KMS-5)与CD70转基因的NIH3T3细胞共同培养后，细胞生长和基因的变化。CD27-CD70相互作用不能诱导任何一种类型的骨髓瘤细胞发生凋亡，而SIVA与CD2？未检测到。基因芯片分析显示CD27-CD70联合作用明显上调外胚层神经皮质1(ENC-1)基因的表达。这些发现表明，CD27的缺失与浆细胞的肿瘤发生之间的关系并不简单。目前尚不清楚CD27的缺失是否导致了细胞凋亡的逃避

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