title: Mouse models in the study of chronic lymphocytic leukemia pathogenesis and therapy.
abstract: Mouse models that recapitulate human malignancy are valuable tools for the elucidation of the underlying pathogenetic mechanisms and for preclinical studies. Several genetically engineered mouse models have been generated, either mimicking genetic aberrations or deregulated gene expression in chronic lymphocytic leukemia (CLL). The usefulness of such models in the study of the human disease may potentially be hampered by species-specific biological differences in the target cell of the oncogenic transformation. Specifically, do the genetic lesions or the deregulated expression of leukemia-associated genes faithfully recapitulate the spectrum of lymphoproliferations in humans? Do the CLL-like lymphoproliferations in the mouse have the phenotypic, histological, genetic, and clinical features of the human disease? Here we compare the various CLL mouse models with regard to disease phenotype, penetrance, and severity. We discuss similarities and differences of the murine lymphoproliferations compared with human CLL. We propose that the Eμ-TCL1 transgenic and 13q14-deletion models that have been comprehensively studied at the levels of leukemia phenotype, antigen-receptor repertoire, and disease course show close resemblance to the human disease. We conclude that modeling CLL-associated genetic dysregulations in mice can provide important insights into the molecular mechanisms of disease pathogenesis and generate valuable tools for the development of novel therapies.
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY;
authors.forename: Giorgia
authors.initials: G
authors.lastname: Simonetti
authors.affiliation: Lymphoid Malignancy Unit, Division of Molecular Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy;
authors.forename: Maria Teresa Sabrina
authors.initials: MT
authors.lastname: Bertilaccio
authors.affiliation: B cell Neoplasia Unit, Division of Molecular Oncology, IRCCS San Raffaele Scientific Institute, Università Vita-Salute San Raffaele, Milan, Italy; Clinical Unit of Lymphoid Malignancies, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy; and.
authors.forename: Paolo
authors.identifier: http://orcid.org/0000-0001-7073-6265
authors.initials: P
authors.lastname: Ghia
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY; Department of Pathology and Cell Biology and Department of Microbiology and Immunology, Columbia University, New York, NY.
authors.forename: Ulf
authors.initials: U
authors.lastname: Klein
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000628:therapy*; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics; D059016:Tumor Microenvironment / Q000235:genetics