Details

Autor(en) / Beteiligte

• Santanam, Urmila
• Zanesi, Nicola
• Efanov, Alexey
• Costinean, Stefan
• Palamarchuk, Alexey
• Hagan, John P.
• Volinia, Stefano
• Alder, Hansjuerg
• Rassenti, Laura
• Kipps, Thomas
• Croce, Carlo M.
• Pekarsky, Yuri

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2010-07, Vol.107 (27), p.12210-12215

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2010

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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.