Mantle cell lymphoma, gene expression in the disease pathogenesis

At the molecular level mantle cell lymphoma (MCL) is characterized by a specific translocation t(11;14) leading to a transcriptional activation of the cyclin D1 gene. Cyclin D1 is a key regulator of the cell cycle and thus its overexpression leads to a proliferation advantage of the cells, which is important in the MCL pathogenesis. Moreover, proliferation activity is an important and the first biological prognostic factor for the MCL prognosis prediction. We developed an optimal approach to analyze quantitatively the cyclin D1 expression level in lymphoma specimens using real-time PCR. We detected the cyclin D1 overexpression in 97% MCL specimens. The developed method supported the MCL differential diagnosis with a high reliability, including a differential diagnosis of extranodal lymphomas. Moreover, the cyclin D1 mRNA expression level measurement also provided an approach to study a key molecule in the MCL pathogenesis at the molecular level. We demonstrated a direct relation between t(11;14), a cyclin D1 mRNA overexpression and a pathologic cyclin D1 protein synthesis in the MCL cells. The cyclin D1 mRNA level also correlated with the mRNA level of proliferation markers implying a quantitative cell cycle regulation by a controlled cyclin D1 level, which controls the proliferation degree, and..