Model of molecular pathogenesis and progression of MCL proposed by Jares et al.8 Ataxia-telangiectasia mutated or cell-cycle checkpoint kinase 2 inactivating mutations have been found in the germline of some MCL patients, and it has been suggested that these mutations may facilitate the lymphoma development. The t(11;14)(q13;q32) translocation occurs in an immature B cell and results in the ectopic and deregulated expression of Cyclin D1, and early expansion of tumor B cells in the mantle zone areas of lymphoid follicles. This translocation is considered a primary pathogenetic event that deregulates the cell-cycle control, probably by overcoming the suppressor effect of retinoblastoma 1 (RB1) and the cell-cycle inhibitor p27. Acquired inactivation of DNA damage response pathways may then facilitate additional oncogenic events and the development of classic MCL. Further genetic alterations may target genes of the cell-cycle and survival regulatory pathways, leading to more proliferative and aggressive variants. Adapted from Jares et al8 with permission.
