Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice
Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice
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DOI：
10.1016/j.ccr.2005.03.037
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发表时间：
2005-05-01
期刊：
影响因子：
50.3
通讯作者：
Dalla-Favera, R
中科院分区：
文献类型：
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作者：
Cattoretti, G;Pasqualucci, L;Dalla-Favera, R
弥漫性大B细胞淋巴瘤（DLBCL）来源于生发中心（GC）B细胞，并显示染色体改变，使GC形成所需的转录抑制因子BCL 6的表达失调。为了研究BCL 6在DLBCL发病机制中的作用，我们通过模拟在人DLBCL中发现的染色体易位，设计了在B细胞中组成型表达BCL 6的小鼠。这些小鼠表现出GC形成增加和GC后分化紊乱，其特征在于同种型转换后浆细胞数量减少。随后，这些小鼠发生淋巴增殖综合征，最终发生淋巴瘤，表现出人DLBCL的典型特征。这些结果定义了BCL 6在DLBCL发病机制中的致癌作用，并提供了这种常见疾病的可靠小鼠模型。
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 lympho-proliferative 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.