Cattoretti Giorgio, Pasqualucci Laura, Ballon Gianna, Tam Wayne, Nandula Subhadra V, Shen Qiong, Mo Tongwei, Murty Vundavalli V, Dalla-Favera Riccardo
Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA.
Cancer Cell. 2005 May;7(5):445-55. doi: 10.1016/j.ccr.2005.03.037.
Diffuse large B cell lymphomas (DLBCL) derive from germinal center (GC) B cells and display chromosomal alterations deregulating the expression of BCL6, a transcriptional repressor required for GC formation. To investigate the role of BCL6 in DLBCL pathogenesis, we have engineered mice that express BCL6 constitutively in B cells by mimicking a chromosomal translocation found in human DLBCL. These mice display increased GC formation and perturbed post-GC differentiation characterized by a decreased number of post-isotype switch plasma cells. Subsequently, these mice develop a lymphoproliferative syndrome that culminates with the development of lymphomas displaying features typical of human DLBCL. These results define the oncogenic role of BCL6 in the pathogenesis of DLBCL and provide a faithful mouse model of this common disease.
弥漫性大B细胞淋巴瘤(DLBCL)起源于生发中心(GC)B细胞,并表现出染色体改变,从而使BCL6的表达失调,BCL6是GC形成所需的一种转录抑制因子。为了研究BCL6在DLBCL发病机制中的作用,我们构建了小鼠模型,通过模拟人类DLBCL中发现的染色体易位,使BCL6在B细胞中持续表达。这些小鼠的GC形成增加且GC后分化受到干扰,其特征是同种型转换后浆细胞数量减少。随后,这些小鼠发展出一种淋巴细胞增殖综合征,并最终发展为具有人类DLBCL典型特征的淋巴瘤。这些结果确定了BCL6在DLBCL发病机制中的致癌作用,并为这种常见疾病提供了一个可靠的小鼠模型。