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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2631-2640. Prepublished online as a Blood First Edition Paper on June 22, 2007; DOI 10.1182/blood-2006-10-053850. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-053850v1 110/7/2631    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cui, J.-W. Articles by Ben-David, Y. Search for Related Content PubMed PubMed Citation Articles by Cui, J.-W. Articles by Ben-David, Y. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 23, 2006 Accepted June 6, 2007 Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation Jiu-Wei Cui, You-Jun Li, Aloke Sarkar, Jeremy Brown, Ye-Hui Tan, Marina Premyslova, Crystal Michaud, Norman Iscove, Guan-Jun Wang, and Yaacov Ben-David* Department of Medical Biophysics, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Canada Dept of Molecular and Cellular Biology, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Canada Department of Hematology, First Hospital of Jilin University, Changchun, China * Corresponding author; email: bendavid{at}sri.utoronto.ca. MicroRNAs (miRNAs) are a newly discovered class of post-transcriptional regulatory noncoding small RNAs. Recent evidence has shown that miRNA mis-expression correlates with progression of various human cancers. Friend erythroleukemia has been used as an excellent system for the identification and characterization of oncogenes and tumor suppressor genes involved in neoplastic transformation. Using this model, we have isolated a novel integration site designated Fli-3, from a Friend murine leukemia virus (F-MuLV)-induced erythroleukemia. The Fli-3 transcription unit is a murine homologue of the human gene, C13orf25 that includes a region encoding the mir-17-92 miRNA cluster. C13orf25 is the target gene of 13q31 chromosomal amplification in human B-cell lymphomas and other malignancies. The erythroleukemias that have acquired either insertional activation or amplification of Fli-3 express higher levels of the primary or mature miRNAs derived from mir-17-92. The ectopic expression of Fli-3 in an erythroblastic cell line switches erythropoeitin (Epo)-induced differentiation to Epo-induced proliferation through activation of the Ras and PI3K pathways. Such a response is associated with alteration in the expression of several regulatory factors, such as Spi-1 and p27 (Kip1). These findings highlight the potential of the Fli-3 encoding mir-17-92 in the development of erythroleukemia and its important role in hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Scherr, L. Venturini, K. Battmer, M. Schaller-Schoenitz, D. Schaefer, I. Dallmann, A. Ganser, and M. Eder Lentivirus-mediated antagomir expression for specific inhibition of miRNA function Nucleic Acids Res., December 3, 2007; 35(22): e149 - e149. [Abstract] [Full Text] [PDF]

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