Increased expression of germinal center-associated nuclear protein RNA-primase is associated with lymphomagenesis
Increased expression of germinal center-associated nuclear protein RNA-primase is associated with lymphomagenesis
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DOI：
10.1158/0008-5472.can-04-3259
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发表时间：
2005-07-01
期刊：
影响因子：
11.2
通讯作者：
Sakaguchi, N
中科院分区：
文献类型：
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作者：
Fujimura, S;Xing, Y;Sakaguchi, N
淋巴瘤的出现含有各种分化阶段特异性分子的异常。在本研究中，我们通过免疫组化分析发现，在人类各种淋巴瘤中，包括套细胞、弥漫性大B细胞和霍奇金淋巴瘤，生发中心B细胞相关GANT异常上调。为了研究GANP在淋巴瘤发生中的作用，我们产生了在免疫球蛋白增强子和启动子控制下表达转基因GANP基因的突变小鼠（ganp-Tg）。Ganp-Tg小鼠在衰老后表现出高的淋巴瘤发生率（29.5%），具有非B/非T细胞表面表型，具有轻微的CD 45 R/B220表达和重排的VH-DH-JH IgH基因座的IG转录物。在ganp-Tg小鼠产生的淋巴瘤表现出类似的病理特征，小鼠网状细胞肿瘤或霍奇金淋巴瘤样病变。单个小鼠的VH序列显示肿瘤从单个克隆或寡克隆增殖，如在人弥漫性大B细胞淋巴瘤和霍奇金淋巴瘤中发现的。这些结果表明，GANP过表达是B淋巴瘤产生的一个致病因素。
Lymphomas arise containing abnormalities of various differentiation stage-specific molecules. In the study reported here, we have shown abnormal up-regulation of germinal center B cell-associated GANT in various human lymphomas including mantle cell, diffuse large B cell, and Hodgkin lymphoma, by immunohistochemical analysis. To study the role of GANP in lymphomagenesis, we generated mutant mice (ganp-Tg) that express the transgenic ganp gene under immunoglobulin enhancer and promoter control. Ganp-Tg mice showed a high incidence of lymphomagenesis (29.5%) after aging with a non-B/non-T cell surface phenotype having slight CD45R/B220 expression and Ig transcripts of rearranged VH-DH-JH IgH loci. Lymphomas generated in ganp-Tg mice displayed similar pathologic characteristics to mouse reticulum cell neoplasm or Hodgkin lymphoma-like lesions. The VH sequences of individual mice showed that the tumors proliferated from a single clone or oligoclones, as is found in human diffuse large B-cell lymphomas and Hodgkin lymphoma. These results suggest that GANP overexpression is a causative factor in the generation of B lymphomas.