Ott M M, Bartkova J, Bartek J, Dürr A, Fischer L, Ott G, Müller-Hermelink H K, Kreipe H
Institute of Pathology, University of Würzburg, Germany.
Blood. 1997 Oct 15;90(8):3154-9.
The cell cycle regulatory protein cyclin D1 is essential for G1-S phase transition in several epithelial and mesenchymal tissues but is apparently not essential in normal mature B cells. An overexpression of cyclin D1 is induced by the chromosomal translocation t(11;14)(q13;q32), which characterizes non-Hodgkin's lymphomas (NHLs) of mantle cell type. We studied 26 cases of mantle cell lymphoma (MCL) for the expression of cyclins D1 and D3. A total of 23 lymphomas showed a nuclear staining for cyclin D1, whereas reactive B cells of residual germinal centers were constantly negative. When compared with cyclin D3, an inverse staining pattern emerged. Whereas the B cells of residual germinal centers reacted strongly positive for cyclin D3, there was low or missing expression of cyclin D3 in MCL cells. In other B-cell lymphomas (n = 55), including chronic lymphocytic leukemia, low-grade lymphomas of mucosa-associated lymphatic tissue, follicular lymphomas, and diffuse large B-cell lymphomas, no cyclin D1 expression could be detected and 89% of these cases displayed cyclin D3 positivity. Lymphoma cell lines harboring the t(11;14) showed cyclin D1 protein but no or very low levels of cyclin D3; three other B-cell lines, a T-cell line, and peripheral blood lymphocytes strongly expressed cyclin D3 and reacted negatively for cyclin D1. We conclude that the chromosomal translocation t(11;14) leads to an abnormal protein expression of cyclin D1 in the tumor cells of MCL and induces a consecutive downregulation of cyclin D3. In contrast to other B-NHLs, cyclin D1 and D3 expression in MCL is not related to the growth fraction.
细胞周期调节蛋白细胞周期蛋白D1对于几种上皮组织和间充质组织中的G1-S期转换至关重要，但在正常成熟B细胞中显然并非必不可少。细胞周期蛋白D1的过表达由染色体易位t(11;14)(q13;q32)诱导，该易位是套细胞型非霍奇金淋巴瘤（NHL）的特征。我们研究了26例套细胞淋巴瘤（MCL）中细胞周期蛋白D1和D3的表达。共有23例淋巴瘤显示细胞周期蛋白D1呈核染色，而残留生发中心的反应性B细胞始终为阴性。与细胞周期蛋白D3相比，出现了相反的染色模式。残留生发中心的B细胞对细胞周期蛋白D3反应强烈阳性，而MCL细胞中细胞周期蛋白D3表达低或缺失。在其他B细胞淋巴瘤（n = 55）中，包括慢性淋巴细胞白血病、黏膜相关淋巴组织低度淋巴瘤、滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤，未检测到细胞周期蛋白D1表达，其中89%的病例显示细胞周期蛋白D3阳性。携带t(11;14)的淋巴瘤细胞系显示细胞周期蛋白D1蛋白，但细胞周期蛋白D3水平无或极低；另外三个B细胞系、一个T细胞系和外周血淋巴细胞强烈表达细胞周期蛋白D3，对细胞周期蛋白D1反应阴性。我们得出结论，染色体易位t(11;14)导致MCL肿瘤细胞中细胞周期蛋白D1异常蛋白表达，并诱导细胞周期蛋白D3的连续下调。与其他B-NHL不同，MCL中细胞周期蛋白D1和D3的表达与生长分数无关。
