Relevance of cyclin D1b expression and CCND1 polymorphism in the pathogenesis of multiple myeloma and mantle cell lymphoma

Background: The CCND1 gene generates two mRNAs ( cyclin D1a and D1b) through an alternative splicing at the site of a common A/ G polymorphism. Cyclin D1a and b proteins differ in their C- terminus, a region involved in protein degradation and sub- cellular localization. Recent data have suggested that cyclin D1b could be a nuclear oncogene. The presence of cyclin D1b mRNA and protein has been studied in two hemopathies in which cyclin D1 could be present: multiple myeloma ( MM) and mantle cell lymphoma ( MCL). The A/ G polymorphism of CCND1 has also been verified in a series of patients. Methods: The expression of cyclin D1 mRNA isoforms has been studied by real- time quantitative PCR; protein isoforms expression, localization and degradation by western blotting. The CCND1 polymorphism was analyzed after sequencing genomic DNA. Results: Cyclin D1 mRNA isoforms a and b were expressed in mantle cell lymphoma ( MCL) and multiple myeloma ( MM). Cyclin D1b proteins were present in MCL, rarely in MM. Importantly, both protein isoforms localized the nuclear and cytoplasmic compartments. They displayed the same short half- life. Thus, the two properties of cyclin D1b recognized as necessary for its transforming activity are missing in MCL. Moreover, CCND1 polymorphism at the exon/ intron boundary had no influence on splicing regulation in MCL cells. Conclusion: Our results support the notion that cyclin D1b is not crucial for the pathogenesis of MCL and MM.