Current treatment standards and future strategies in mantle cell lymphoma

Abstract

The genetic hallmark of mantle cell lymphoma (MCL) is the translocation t(11;14)(q13;q32), which can be detected by classical cytogenetics or FISH analysis resulting in overexpression of the cell cycle regulator protein cyclin D1, which may be detected by immunostaining in the large majority of cases. It is still under debate whether cases of atypical CLL with t(11;14) represent a different disease entity. On the other hand, t(11;14)-negative MCL cases have been reported recently, which, however, display a clinical course similar to that of classical MCL [1]. In a substantial proportion of MCL cases, decreased levels of inhibitors of CDK4 and CDK6, such as p16, can be detected. Typically those cases are characterized by blastoid morphology and even more aggressive clinical behavior. Interestingly the gene locus on 9p21 encodes not only p16, but also another protein p16; decreased levels of p16 result in increased MDM2 (mouse double minute 2 homolog)-mediated p53 degradation. Furthermore ATM (ataxia teleangiectasia mutated) gene on chromosome 11q22–23 is mutated in up to 75% of cases also resulting in impaired p53-mediated cell cycle arrest, DNA repair and apoptosis. Highly interesting data were obtained by gene expression analysis. Certain proliferation signatures identified patient subsets that differed by >5 years in overall survival [1]. Taken together the pathogenesis of MCL is characterized by simultaneous disruption of cell cycle regulation and DNA damage response [2].