title: Mantle cell lymphoma: a biological and therapeutic paradigm.
abstract: Recent classifications of non-Hodgkin's lymphomas (NHL) have strictly individualized mantle cell lymphoma (MCL) on the basis of a combination of morphologic, immunophenotypic, and cytogenetic criteria. This clinicopathological entity now appears to be a biological and therapeutic model for the understanding and treatment of hematologic malignancies. The lymphomogenesis of MCL could be explained by a series of genetic abnormalities which occur at different steps of the disease: (1) mutation and/or loss of the ATM gene in centrocytic cells of the follicle mantle of lymph nodes, leading to the loss of ATM function, particularly involved during the V(D)J recombination process; (2) a t(11;14)(q13;q32) translocation which induces a constitutive Bcl-1/PRAD1/CCND1 expression, responsible for cell cycle activation of centrocytic cells characteristic of typical MCL; and (3) secondary additional chromosomal aberrations, such as a p53 mutation, observed in blastic transformation of MCL. Despite the evaluation of a number of treatment modalities, the optimal management of MCL has not yet been defined: (1) conventional and intensified chemotherapy and monoclonal anti-CD20 antibody therapy appear to be effective for the improvement of response rates and event-free or overall survivals; (2) combinations of different treatment modalities must be tested to modify the natural dismal outcome of the disease; and (3) innovative approaches should be developed. From this point of view, all these considerations offer a fine opportunity for extensive medical reflection.
authors.affiliation: Department of Hematology, Service d'Hématologie, Institut Curie, Paris, France. didier.decaudin@curie.net
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins; D006801:Humans; D007167:Immunotherapy; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases