Cyclin D1 expression in B-cell lymphomas

Abstract

Cyclin D1, an important component of cell cycle machinery and a protein with known oncogenic potential, is downregulated in normal mature B lymphocytes. Its expression detected in a number of malignancies, including B-cell lymphomas, may be important for oncogenesis. In our work, we determined the level of cyclin D1 expression in various B-cell lymphomas (i.e., mantle cell lymphoma, B-cell chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and compared it with normal B cells. For cyclin D1 level evaluation, the real-time quantitative polymerase chain reaction data was normalized. We tested five reference genes for stability on our sample set and using the three most stable ones (YWHAZ, ubiquitin c, and HPRT) obtained rather small intra-group variance for cyclin D1 expression in most lymphomas. This allowed their statistically significant ranking according to cyclin D1 expression level. Median values of normalized cyclin D1 expression determined by real-time quantitative polymerase chain reaction were 1.32 for mantle cell lymphoma, 0.02 for B-cell chronic lymphocytic leukemia, 0.009 for diffuse large B-cell lymphoma, 0.004 for marginal zone lymphoma, 0.002 for follicular lymphoma compared with 0.0003 for reactive lymphoid tissue, and 0.00004 for sorted B cells of healthy donors. Our data demonstrate that mantle cell lymphoma, a lymphoma with t(11;14)(q13;q32) translocation, has the level of cyclin D1 increased by four orders of magnitude, while other B-cell lymphomas without t(11;14)(q13;q32) translocation still have the level of cyclin D1 significantly elevated above that of normal lymphocytes (2 orders for B-cell chronic lymphocytic leukemia and an order for other lymphomas) and suggests more than one method of its upregulation in malignant B cells.