SEARCH:   Advanced

Blood, 15 January 2008, Vol. 111, No. 2, pp. 816-828. Prepublished online as a Blood First Edition Paper on October 9, 2007; DOI 10.1182/blood-2007-05-090472. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-090472v1 111/2/816    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Eiring, A. M. Articles by Perrotti, D. Search for Related Content PubMed PubMed Citation Articles by Eiring, A. M. Articles by Perrotti, D. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis Anna M. Eiring1, Paolo Neviani1, Ramasamy Santhanam1, Joshua J. Oaks1, Ji Suk Chang1, Mario Notari1, William Willis1, Carlo Gambacorti-Passerini2, Stefano Volinia1,3, Guido Marcucci1, Michael A. Caligiuri1, Gustavo W. Leone1, and Danilo Perrotti1 1 Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH; 2 University of Milano Bicocca, S. Gerardo Hospital, Monza, Italy; and 3 Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy Several RNA binding proteins (RBPs) have been implicated in the progression of chronic myelogenous leukemia (CML) from the indolent chronic phase to the aggressively fatal blast crisis. In the latter phase, expression and function of specific RBPs are aberrantly regulated at transcriptional or posttranslational levels by the constitutive kinase activity of the BCR/ABL oncoprotein. As a result, altered expression/function of RBPs leads to increased resistance to apoptotic stimuli, enhanced survival, growth advantage, and differentiation arrest of CD34+ progenitors from patients in CML blast crisis. Here, we identify the mRNAs bound to the hnRNP-A1, hnRNP-E2, hnRNP-K, and La/SSB RBPs in BCR/ABLtransformed myeloid cells. Interestingly, we found that the mRNA encoding the transcription factor E2F3 associates to hnRNP-A1 through a conserved binding site located in the E2F3 3' untranslated region (UTR). E2F3 levels were up-regulated in CML-BCCD34+ in a BCR/ABL kinase– and hnRNP-A1 shuttling–dependent manner. Moreover, by using shRNA-mediated E2F3 knock-down and BCR/ABL-transduced lineage-negative bone marrow cells from E2F3+/+ and E2F3–/– mice, we show that E2F3 expression is important for BCR/ABL clonogenic activity and in vivo leukemogenic potential. Thus, the complexity of the mRNA/RBP network, together with the discovery of E2F3 as an hnRNP-A1–regulated factor, outlines the relevant role played by RBPs in posttranscriptional regulation of CML development and progression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Gao, A. Howard, K. Ban, and J. Chandra Oxidative Stress Promotes Transcriptional Up-regulation of Fyn in BCR-ABL1-expressing Cells J. Biol. Chem., March 13, 2009; 284(11): 7114 - 7125. [Abstract] [Full Text] [PDF] C. H. Jamieson Chronic Myeloid Leukemia Stem Cells Hematology, January 1, 2008; 2008(1): 436 - 442. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020