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

Department of Molecular Virology, Ohio State University School of Medicine, Ohio State University, Columbus, OH 43210, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 07/2010; 107(27):12210-5. DOI: 10.1073/pnas.1007186107
Source: PubMed

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.

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Available from: Stefan Costinean, Feb 03, 2015
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    • "Although aberrant expression of some miRNAs occurred in CRC metastasis, such as miR-17, miR-19a and miR-21 (Zhang et al, 2012), miR-31 (Wang et al, 2010), miR-103 and miR-107 (Chen et al, 2012), miR-143 and miR-145 (Arndt et al, 2009) and miR-200 family (Hur et al, 2012), novel candidates with a definite molecular mechanism in promoting CRC metastasis need to be further explored. It was reported that the dysregulation of miR-29a performed a diverse function in different types of cancer (Gebeshuber et al, 2009; Muniyappa et al, 2009; Eyholzer et al, 2010; Santanam et al, 2010; Cui et al, 2011; Kong et al, 2011; Teichler et al, 2011). It was previously believed that high serum expression of miR-29a in CRC patients was correlated with liver metastasis, and was proposed as a novel biomarker for early and noninvasive diagnosis of CRC (Wang and Gu, 2012). "
    W Tang · Y Zhu · J Gao · J Fu · C Liu · Y Liu · C Song · S Zhu · Y Leng · G Wang · W Chen · P Du · S Huang · X Zhou · J Kang · L Cui
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    British Journal of Cancer 11/2013; 110(2). DOI:10.1038/bjc.2013.724 · 4.82 Impact Factor
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    • "), a miRNA associated with indolent B cell chronic lymphocytic leukemia . The transgenic expression of miR-29 in B cells and HSCs leads to CLL and acute myeloid leukemia (AML), respectively (Han et al. 2010; Santanam et al. 2010), which suggests that miR-B4 could be important for BLV-induced B cell tumorigenesis. Interestingly, the EBV miRNA miR-BART1-3p shares its minimal seed sequence (nts 2–7) with miR-29, suggesting that at least some targets are likely to be common for miR-BART1-3p and miR-29 (Skalsky et al. 2012). "
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    Current topics in microbiology and immunology 01/2013; 371:201-227. DOI:10.1007/978-3-642-37765-5_8 · 3.47 Impact Factor
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    • "Members of this family have been shown to be silenced or down - regulated in many different types of cancer and have subsequently been attributed tumor - suppressing properties , although exceptions have been described where miR - 29s have tumor - promoting functions ( Pekarsky and Croce 2010 ; Santanam et al . 2010 ) . Experimental evidence suggest that putative targets of miR - 29 family includes , the anti - apoptotic factor BCL - 2 ( Mott et al . 2007 ) , T - cell leukemia / lymphoma protein 1A ( TCL1A ) oncogene , found to be disrupted in many T - cell leukemias ( Pekarsky et al . 2006 ) and DNA methyltransferasesDNMT3A and DNMT3B , which are "
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