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Blood, 1 August 2005, Vol. 106, No. 3, pp. 871-878. Prepublished online as a Blood First Edition Paper on April 19, 2005; DOI 10.1182/blood-2004-08-3056. This Article Full Text (PDF) All Versions of this Article: 2004-08-3056v1 106/3/871    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 Shafarenko, M. Articles by Hoffman, B. Search for Related Content PubMed PubMed Citation Articles by Shafarenko, M. Articles by Hoffman, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 5, 2004 Accepted April 5, 2005 Egr-1 abrogates the block imparted by c-Myc on terminal M1 myeloid differentiation Marianna Shafarenko, Dan A Liebermann, and Barbara Hoffman* Fels Institute for Cancer Research and Molecular Biology, and Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA, USA * Corresponding author; email: hoffman{at}temple.edu. Both deregulated growth and blocks in differentiation cooperate in the multistage process of leukemogenesis. Thus, understanding functional interactions between genes that regulate normal blood cell development, including cell growth and differentiation, and how their altered expression contributes to leukemia, is important for rational drug design. Previously, we have shown that the zinc finger transcription factor Egr-1 plays a role in monocytic differentiation. Ectopic expression of Egr-1 in M1 myeloblastic leukemia cells was observed to activate the macrophage differentiation program in the absence of the differentiation inducer IL-6, and to promote terminal differentiation in its presence. In addition, we have shown that deregulated expression of the proto-oncogene c-myc blocks the myeloid terminal differentiation program. Here we show that restoring expression of Egr-1 in M1 cells that express deregulated c-Myc abrogates the c-Myc block in terminal differentiation, resulting in cells that undergo functional macrophage maturation. However, there is an absence of both growth arrest and cell adhesion. In addition, Egr-1 expression decreased M1myc leukemogenicity in vivo. These findings indicate that Egr-1 can act as a tumor suppressor gene, and suggest that Egr-1 and/or Egr-1 targets may provide important tools for differentiation therapy in certain leukemic phenotypes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. D. Licht What unleashes aberrant gene regulation in acute promyelocytic leukemia? Blood, February 1, 2007; 109(3): 857 - 857. [Full Text] [PDF] R. Schippert, E. Burkhardt, M. Feldkaemper, and F. Schaeffel Relative Axial Myopia in Egr-1 (ZENK) Knockout Mice Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 11 - 17. [Abstract] [Full Text] [PDF]

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