Báez Alicia, Piruat José I, Caballero-Velázquez Teresa, Sánchez-Abarca Luís I, Álvarez-Laderas Isabel, Barbado M Victoria, García-Guerrero Estefanía, Millán-Uclés África, Martín-Sánchez Jesús, Medrano Mayte, Pérez-Simón José Antonio
Department of Hematology, University Hospital Virgen del Rocío, Institute of Biomedicine of Seville (IBIS), CSIC, Universidad de Sevilla Seville, Spain.
Am J Cancer Res. 2014 Dec 15;5(1):386-95. eCollection 2015.
Memory B cells (MBCs) remain in a quiescent state for years, expressing pro-survival and anti-apoptotic factors while repressing cell proliferation and activation genes. During their differentiation into plasma cells (PCs), their expression pattern is reversed, with a higher expression of genes related to cell proliferation and activation, and a lower expression of pro-survival genes. To determine whether myelomatous PCs (mPCs) share characteristics with normal PCs and MBCs and to identify genes involved in the pathophysiology of multiple myeloma (MM), we compared gene expression patterns in these three cell sub-types. We observed that mPCs had features intermediate between those of MBCs and normal PCs, and identified 3455 genes differentially expressed in mPCs relative to normal PCs but with a similar expression pattern to that in MBCs. Most of these genes are involved in cell death and survival, cell growth and proliferation and protein synthesis. According to our findings, mPCs have a gene expression pattern closer to a MBC than a PC with a high expression of genes involved in cell survival. These genes should be physiologically inactivated in the transit from MBC to PC, but remain overexpressed in mPCs and thus may play a role in the pathophysiology of the disease.
记忆B细胞（MBCs）会保持数年的静止状态，表达促生存和抗凋亡因子，同时抑制细胞增殖和激活基因。在它们分化为浆细胞（PCs）的过程中，其表达模式会逆转，与细胞增殖和激活相关的基因表达较高，而促生存基因的表达较低。为了确定骨髓瘤浆细胞（mPCs）是否与正常浆细胞和记忆B细胞具有共同特征，并鉴定参与多发性骨髓瘤（MM）病理生理学的基因，我们比较了这三种细胞亚型的基因表达模式。我们观察到，骨髓瘤浆细胞具有介于记忆B细胞和正常浆细胞之间的特征，并鉴定出3455个相对于正常浆细胞在骨髓瘤浆细胞中差异表达但与记忆B细胞具有相似表达模式的基因。这些基因大多参与细胞死亡和生存、细胞生长和增殖以及蛋白质合成。根据我们的研究结果，骨髓瘤浆细胞的基因表达模式更接近记忆B细胞而非浆细胞，与细胞生存相关的基因高表达。这些基因在从记忆B细胞向浆细胞转变的过程中应在生理上失活，但在骨髓瘤浆细胞中仍过度表达，因此可能在该疾病的病理生理学中发挥作用。
