1. Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression
- Author
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Urmila Santanam, Nicola Zanesi, Alexey Efanov, Stefan Costinean, Alexey Palamarchuk, John P. Hagan, Stefano Volinia, Hansjuerg Alder, Laura Rassenti, Thomas Kipps, Carlo M. Croce, and Yuri Pekarsky
- Subjects
Transgene ,Chronic lymphocytic leukemia ,Antigens, CD19 ,chemical and pharmacologic phenomena ,Mice, Transgenic ,Biology ,CD5 Antigens ,Transgenic ,Immunophenotyping ,Flow cytometry ,Mice ,Antigen ,immune system diseases ,hemic and lymphatic diseases ,microRNA ,medicine ,Animals ,Humans ,Lymphocyte Count ,Antigens ,Chronic ,Leukemic ,Regulation of gene expression ,B-Lymphocytes ,Leukemia ,Multidisciplinary ,CD19 ,medicine.diagnostic_test ,Gene Expression Regulation, Leukemic ,Animal ,Reverse Transcriptase Polymerase Chain Reaction ,B-Cell ,Biological Sciences ,Flow Cytometry ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Lymphocytic ,CD5 ,Disease Models, Animal ,MicroRNAs ,Gene Expression Regulation ,Disease Models ,Immunology ,Cancer research ,Spleen - 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 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.
- Published
- 2010
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