SEARCH:   Advanced

Blood, 15 January 2007, Vol. 109, No. 2, pp. 747-755. Prepublished online as a Blood First Edition Paper on September 5, 2006; DOI 10.1182/blood-2006-03-011106. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-011106v1 109/2/747    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 Kharas, M. G. Articles by Fruman, D. A. Search for Related Content PubMed PubMed Citation Articles by Kharas, M. G. Articles by Fruman, D. A. Related Collections Oncogenes and Tumor Suppressors Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA KLF4 suppresses transformation of pre-B cells by ABL oncogenes Michael G. Kharas1, Isharat Yusuf1, Vanessa M. Scarfone1, Vincent W. Yang2, Julia A. Segre3, Claudia S. Huettner4, and David A. Fruman1,5, 1 Department of Molecular Biology and Biochemistry, University of California–Irvine; 2 Department of Medicine, Emory University, Atlanta, GA; 3 National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; 4 The Blood Center of SE Wisconsin, Milwaukee; and 5 Center for Immunology, University of California–Irvine Genes that are strongly repressed after B-cell activation are candidates for being inactivated, mutated, or repressed in B-cell malignancies. Krüppel-like factor 4 (Klf4), a gene down-regulated in activated murine B cells, is expressed at low levels in several types of human B-cell lineage lymphomas and leukemias. The human KLF4 gene has been identified as a tumor suppressor gene in colon and gastric cancer; in concordance with this, overexpression of KLF4 can suppress proliferation in several epithelial cell types. Here we investigate the effects of KLF4 on pro/pre–B-cell transformation by v-Abl and BCR-ABL, oncogenes that cause leukemia in mice and humans. We show that overexpression of KLF4 induces arrest and apoptosis in the G1 phase of the cell cycle. KLF4-mediated death, but not cell-cycle arrest, can be rescued by Bcl-XL overexpression. Transformed pro/pre-B cells expressing KLF4 display increased expression of p21CIP and decreased expression of c-Myc and cyclin D2. Tetracycline-inducible expression of KLF4 in B-cell progenitors of transgenic mice blocks transformation by BCR-ABL and depletes leukemic pre-B cells in vivo. Collectively, our work identifies KLF4 as a putative tumor suppressor in B-cell malignancies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Yusuf, M. G. Kharas, J. Chen, R. Q. Peralta, A. Maruniak, P. Sareen, V. W. Yang, K. H. Kaestner, and D. A. Fruman KLF4 is a FOXO target gene that suppresses B cell proliferation Int. Immunol., May 1, 2008; 20(5): 671 - 681. [Abstract] [Full Text] [PDF] J. G. Harb, B. I. Chyla, and C. S. Huettner Loss of Bcl-x in Ph+ B-ALL increases cellular proliferation and does not inhibit leukemogenesis Blood, April 1, 2008; 111(7): 3760 - 3769. [Abstract] [Full Text] [PDF] J. Klaewsongkram, Y. Yang, S. Golech, J. Katz, K. H. Kaestner, and N.-p. Weng Kruppel-Like Factor 4 Regulates B Cell Number and Activation-Induced B Cell Proliferation J. Immunol., October 1, 2007; 179(7): 4679 - 4684. [Abstract] [Full Text] [PDF] K. L. Good and S. G. Tangye Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses PNAS, August 14, 2007; 104(33): 13420 - 13425. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020