CYCLIN D1 EXPRESSION IN MANTLE CELL LYMPHOMA IS ACCOMPANIED BY DOWN-REGULATION OF CYCLIN D3 AND IS NOT RELATED TO THE PROLIFERATIVE ACTIVITY

The cell cycle regulatory protein cyclin D1 is essential for G1-S phas e transition in several epithelial and mesenchymal tissues but is appa rently not essential in normal mature B cells. An overexpression of cy clin D1 is induced by the chromosomal translocation t(11;14)(q13;q32), which characterizes non-Hodgkin's lymphomas (NHLs) of mantle cell typ e. We studied 26 cases of mantle cell lymphoma (MCL) for the expressio n of cyclins D1 and D3. A total of 23 lymphomas showed a nuclear stain ing for cyclin D1, whereas reactive B cells of residual germinal cente rs were constantly negative. When compared with cyclin D3, an inverse staining pattern emerged, Whereas the B cells of residual germinal cen ters 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 mu cosa-associated lymphatic tissue, follicular lymphomas, and diffuse la rge B-cell lymphomas, no cyclin D1 expression could be detected and 89 % of these cases displayed cyclin D3 positivity. Lymphoma cell lines h arboring the t(11;14) showed cyclin D1 protein but no or very low leve ls of cyclin D3; three other B-cell lines, a T-cell line, and peripher al blood lymphocytes strongly expressed cyclin D3 and reacted negative ly 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 r elated to the growth fraction. (C) 1997 by The American Society of Hem atology.