title: Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression.
abstract: B-cell chronic lymphocytic leukemia (B-CLL), the most common leukemia in the Western world, occurs in two forms, aggressive (showing for the most part high ZAP-70 expression and unmutated IgH V(H)) and indolent (showing low ZAP-70 expression and mutated IgH V(H)). We found that miR-29a is up-regulated in indolent human B-CLL as compared with aggressive B-CLL and normal CD19(+) B cells. To study the role of miR-29 in B-CLL, we generated Emu-miR-29 transgenic mice overexpressing miR-29 in mouse B cells. Flow cytometric analysis revealed a markedly expanded CD5(+) population in the spleen of these mice starting at 2 mo of age, with 85% (34/40) of miR-29 transgenic mice exhibiting expanded CD5(+) B-cell populations, a characteristic of B-CLL. On average, 50% of B cells in these transgenic mice were CD5 positive. At 2 y of age the mice showed significantly enlarged spleens and an increase in the CD5(+) B-cell population to approximately 100%. Of 20 Emu-miR-29 transgenic mice followed to 24-26 mo of age, 4 (20%) developed frank leukemia and died of the disease. These results suggest that dysregulation of miR-29 can contribute to the pathogenesis of indolent B-CLL.
authors.affiliation: Department of Molecular Virology, Ohio State University School of Medicine, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Urmila
authors.initials: U
authors.lastname: Santanam
authors.forename: Nicola
authors.initials: N
authors.lastname: Zanesi
authors.forename: Alexey
authors.initials: A
authors.lastname: Efanov
authors.forename: Stefan
authors.initials: S
authors.lastname: Costinean
authors.forename: Alexey
authors.initials: A
authors.lastname: Palamarchuk
authors.forename: John P
authors.initials: JP
authors.lastname: Hagan
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.forename: Laura
authors.initials: L
authors.lastname: Rassenti
authors.forename: Thomas
authors.initials: T
authors.lastname: Kipps
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pekarsky
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D018941:Antigens, CD19; D018956:CD5 Antigens; C532045:MIRN29a microRNA, human; D035683:MicroRNAs