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 VH) and indolent (showing low ZAP-70 expression and mutated IgH VH). 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 Eμ-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 ∼100%. Of 20 Eμ-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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- July 2010
- DOI:
- 10.1073/pnas.1007186107
- Bibcode:
- 2010PNAS..10712210S