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Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12210-5. doi: 10.1073/pnas.1007186107. Epub 2010 Jun 21.

Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression.

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  • 1Department of Molecular Virology, Ohio State University School of Medicine, Ohio State University, Columbus, OH 43210, USA.

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.

PMID:
20566844
[PubMed - indexed for MEDLINE]
PMCID:
PMC2901490
Free PMC Article

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