Implication of cyclin D1 in malignant lymphoma

The chromosomal translocation t(11;14)(q13;q32) is observed in a number of lymphoid malignancies but is specifically associated with a particular subtype of non-Hodgkin's lymphoma called mantle cell lymphoma, where it is observed in up to 70% of cases. This translocation juxtaposes IGH sequences at 14q32 to a region variously termed BCL1/PRAD1 at 11q13, on the derivative chromosome 11. Detailed molecular analysis identified BCL1 to be a gene coding for the G1 cyclin, cyclin D1, which is an important regulator of the G1/S transition of the cell cycle. Cyclin D1 overexpression is observed in a vast majority of mantle cell lymphoma and lymphoid malignancies with 11q13 rearrangement, thereby confirming BCL1, now referred to as CCND1, as the gene targeted by these rearrangements. In this review, following a brief discussion of the role of cyclin D1 in cell cycle regulation, we discuss the mechanisms and pathogenetic impact of cyclin D1 activation in lymphoproliferative disorders with 11q13 rearrangement. We also review a number of the diagnostic strategies available for detection of CCND1 rearrangement/overexpression, with particular emphasis on applications for mantle cell lymphoma.