CYCLIN D2 OVEREXPRESSION RECAPITULATES MANTLE CELL LYMPHOMA IN MICE

Mantle cell lymphoma (MCL) is a highly aggressive subtype of B-cell lymphoma that is characterized by a poor response to current treatment regimens. Most MCLs carry a prototypical translocation, t(11;14), which juxtaposes the CCND1 gene towards the immunoglobulin heavy chain (IGH) locus, resulting in cyclin D1 overexpression. Strikingly, MCL has not been recapitulated in transgenic mouse models of Ccnd1 overexpression alone. Notably, a subset of MCL patients are cyclin D1 negative but instead overexpress cyclin D2 (encoded by CCND2)as a consequence of recurrent genomic rearrangements involving the CCND2 locus.