Cyclin D1 Expression in Mantle Cell Lymphoma Is Accompanied by Downregulation of Cyclin D3 and Is Not Related to the Proliferative Activity

Abstract

Abstract 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.