No evidence of cell cycle dysregulation in mantle cell lymphoma in vivo.

Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14)(q13;q32) leading to an overexpression of cyclin D1, a mediator of G1-S phase transition. Thus MCL is regarded as a paradigm of lymphoma with a dysregulated cell cycle. The proliferation rate of MCL is in fact a strong predictor of outcome. We analyzed proteins that are expressed at defined cell cycle phases, such as Ki67, survivin and phosphorylated histone H3 as well as cyclin D1, p53 and p27, on the cellular level by immunofluorescence double stainings in MCL biopsy specimens. Unexpectedly, we did not detect a shortening of early phases in MCL in vivo. Despite the control of the immunoglobulin enhancer, cyclin D1 was expressed in a cell cycle-dependent manner. However, the proliferating Ki67-positive tumor cells expressed low amounts of cyclin D1. Therefore, the expression of cyclin D1 appears not to be the driving factor behind the total proliferation rate of MCL.