Montes-Moreno Santiago, Roncador Giovanna, Maestre Lorena, Martínez Nerea, Sanchez-Verde Lydia, Camacho Francisca I, Cannata Jimena, Martinez-Torrecuadrada Jorge L, Shen Yulei, Chan Wing C, Piris Miguel A
Lymphoma Group, Spanish National Cancer Centre (CNIO), Madrid, Spain.
Blood. 2008 Jan 1;111(1):351-8. doi: 10.1182/blood-2007-06-094151. Epub 2007 Sep 26.
GCET1 (germinal center B cell-expressed transcript-1) gene codes for a serpin expressed in germinal center (GC) B cells. Following the observation that follicular lymphoma cases exhibit an increased level of Gcet1 expression, compared with follicular hyperplasia, we have characterized Gcet1 protein expression in human tissues, cell lines, and a large series of lymphomas. To this end, we have performed immunohistochemical and Western blot analyses using a newly generated monoclonal antibody that is reactive in paraffin-embedded tissues. Our results demonstrate that Gcet1 is expressed exclusively by neoplasms hypothetically to be arrested at the GC stage of differentiation, including follicular lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and a subset of diffuse large B-cell lymphoma, T-cell/histiocyte rich B-cell lymphoma, and Burkitt lymphoma. Within these tumors, Gcet-1 protein expression is restricted to a subset of GC B cells, establishing the existence of a distinct heterogeneity among normal and neoplastic GC B cells. None of the other B-cell lymphomas, that is, chronic lymphocytic leukemia, splenic marginal zone lymphoma, and mantle cell lymphoma, was Gcet1(+), which underlines the potential utility of Gcet1 expression in lymphoma diagnosis. The results of RNA and protein expression should prompt further investigation into the role of Gcet1 in regulating B-cell survival.
GCET1(生发中心B细胞表达转录本-1)基因编码一种在生发中心(GC)B细胞中表达的丝氨酸蛋白酶抑制剂。在观察到滤泡性淋巴瘤病例与滤泡增生相比Gcet1表达水平升高后,我们对Gcet1蛋白在人体组织、细胞系和大量淋巴瘤中的表达进行了特征分析。为此,我们使用一种新产生的在石蜡包埋组织中有反应性的单克隆抗体进行了免疫组织化学和蛋白质印迹分析。我们的结果表明,Gcet1仅由假设处于分化GC阶段停滞的肿瘤表达,包括滤泡性淋巴瘤、结节性淋巴细胞为主型霍奇金淋巴瘤以及弥漫性大B细胞淋巴瘤、富于T细胞/组织细胞的B细胞淋巴瘤和伯基特淋巴瘤的一个子集。在这些肿瘤中,Gcet-1蛋白表达局限于GC B细胞的一个子集,证实了正常和肿瘤性GC B细胞之间存在明显的异质性。其他B细胞淋巴瘤,即慢性淋巴细胞白血病、脾边缘区淋巴瘤和套细胞淋巴瘤,均无Gcet1阳性,这突出了Gcet1表达在淋巴瘤诊断中的潜在效用。RNA和蛋白质表达结果应促使进一步研究Gcet1在调节B细胞存活中的作用。