SEARCH:   Advanced

Blood, 1 March 2004, Vol. 103, No. 5, pp. 1676-1684. Prepublished online as a Blood First Edition Paper on November 6, 2003; DOI 10.1182/blood-2003-07-2202. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2202v1 103/5/1676    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 Dorsam, S. T. Articles by Lawrence, H. J. Search for Related Content PubMed PubMed Citation Articles by Dorsam, S. T. Articles by Lawrence, H. J. Related Collections Hematopoiesis and Stem Cells Neoplasia Gene Expression Genomics Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The transcriptome of the leukemogenic homeoprotein HOXA9 in human hematopoietic cells Sheri Tinnell Dorsam, Christina M. Ferrell, Glenn P. Dorsam, Mika Kakefuda Derynck, Ulka Vijapurkar, Daniel Khodabakhsh, Bonnie Pau, Hillary Bernstein, Christopher M. Haqq, Corey Largman, and H. Jeffrey Lawrence From the Department of Medicine, Veterans Affairs Medical Center; Department of Medicine and UCSF Comprehensive Cancer Center, University of California at San Francisco. Hematopoietic defects in HOXA9–/– mice demonstrate a key role for this homeoprotein in blood cell development. Conversely, enforced HOXA9 expression is leukemogenic in mice, and HOXA9 is frequently activated in human acute myeloid leukemia (AML). Although HOXA9 is thought to function as a transcription factor, few downstream targets have been identified. We searched for early HOXA9 target genes by using a transient overexpression strategy in 3 hematopoietic cell lines (2 myeloid, 1 lymphoid). cDNA microarray analyses identified 220 genes whose expression was modulated at least 2-fold. Expression signatures in myeloid and lymphoid cells demonstrated that HOXA9 functions as both an activator and repressor of a variety of genes in cell-specific patterns suggesting that the transcriptional effects of HOXA9 are largely dependent on the cell context. Transient transcription assays and target gene expression patterns in HOXA9–/– marrow cells imply that we have identified direct physiologic targets. Many target genes are expressed in CD34+ stem cells or are members of gene families involved in proliferation or myeloid differentiation. Expression of 14 HOXA9 target genes correlated with high-level HOXA9 expression in primary AML. These data suggest that many genes identified in this survey may mediate the biologic effects of HOXA9 in normal and leukemic hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-L. Hu, S. Fong, C. Ferrell, C. Largman, and W.-F. Shen HOXA9 Modulates Its Oncogenic Partner Meis1 To Influence Normal Hematopoiesis Mol. Cell. Biol., September 15, 2009; 29(18): 5181 - 5192. [Abstract] [Full Text] [PDF] R. Farras, V. Baldin, S. Gallach, C. Acquaviva, G. Bossis, I. Jariel-Encontre, and M. Piechaczyk JunB Breakdown in Mid-/Late G2 Is Required for Down-Regulation of Cyclin A2 Levels and Proper Mitosis Mol. Cell. Biol., June 15, 2008; 28(12): 4173 - 4187. [Abstract] [Full Text] [PDF] Y.-L. Hu, E. Passegue, S. Fong, C. Largman, and H. J. Lawrence Evidence that the Pim1 kinase gene is a direct target of HOXA9 Blood, June 1, 2007; 109(11): 4732 - 4738. [Abstract] [Full Text] [PDF] P. A. Reynolds, M. Sigaroudinia, G. Zardo, M. B. Wilson, G. M. Benton, C. J. Miller, C. Hong, J. Fridlyand, J. F. Costello, and T. D. Tlsty Tumor Suppressor p16INK4A Regulates Polycomb-mediated DNA Hypermethylation in Human Mammary Epithelial Cells J. Biol. Chem., August 25, 2006; 281(34): 24790 - 24802. [Abstract] [Full Text] [PDF] A. L. Brown, C. R. Wilkinson, S. R. Waterman, C. H. Kok, D. G. Salerno, S. M. Diakiw, B. Reynolds, H. S. Scott, A. Tsykin, G. F. Glonek, et al. Genetic regulators of myelopoiesis and leukemic signaling identified by gene profiling and linear modeling J. Leukoc. Biol., August 1, 2006; 80(2): 433 - 447. [Abstract] [Full Text] [PDF] J. L. Hess, C. B. Bittner, D. T. Zeisig, C. Bach, U. Fuchs, A. Borkhardt, J. Frampton, and R. K. Slany c-Myb is an essential downstream target for homeobox-mediated transformation of hematopoietic cells Blood, July 1, 2006; 108(1): 297 - 304. [Abstract] [Full Text] [PDF] G. G. Wang, M. P. Pasillas, and M. P. Kamps Persistent Transactivation by Meis1 Replaces Hox Function in Myeloid Leukemogenesis Models: Evidence for Co-Occupancy of Meis1-Pbx and Hox-Pbx Complexes on Promoters of Leukemia-Associated Genes Mol. Cell. Biol., May 15, 2006; 26(10): 3902 - 3916. [Abstract] [Full Text] [PDF] H. J. Lawrence, J. Christensen, S. Fong, Y.-L. Hu, I. Weissman, G. Sauvageau, R. K. Humphries, and C. Largman Loss of expression of the Hoxa-9 homeobox gene impairs the proliferation and repopulating ability of hematopoietic stem cells Blood, December 1, 2005; 106(12): 3988 - 3994. [Abstract] [Full Text] [PDF] L. Bullinger and P. J.M. Valk Gene Expression Profiling in Acute Myeloid Leukemia J. Clin. Oncol., September 10, 2005; 23(26): 6296 - 6305. [Abstract] [Full Text] [PDF] H. Chen, E. Rubin, H. Zhang, S. Chung, C. C. Jie, E. Garrett, S. Biswal, and S. Sukumar Identification of Transcriptional Targets of HOXA5 J. Biol. Chem., May 13, 2005; 280(19): 19373 - 19380. [Abstract] [Full Text] [PDF] B. B. Menon, N. J. Sarma, S. Pasula, S. J. Deminoff, K. A. Willis, K. E. Barbara, B. Andrews, and G. M. Santangelo Reverse recruitment: The Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation PNAS, April 19, 2005; 102(16): 5749 - 5754. [Abstract] [Full Text] [PDF] L. Bei, Y. Lu, and E. A. Eklund HOXA9 Activates Transcription of the Gene Encoding gp91Phox during Myeloid Differentiation J. Biol. Chem., April 1, 2005; 280(13): 12359 - 12370. [Abstract] [Full Text] [PDF] K. Kirito, N. Fox, and K. Kaushansky Thrombopoietin Induces HOXA9 Nuclear Transport in Immature Hematopoietic Cells: Potential Mechanism by Which the Hormone Favorably Affects Hematopoietic Stem Cells Mol. Cell. Biol., August 1, 2004; 24(15): 6751 - 6762. [Abstract] [Full Text] [PDF] W. Wagner, A. Ansorge, U. Wirkner, V. Eckstein, C. Schwager, J. Blake, K. Miesala, J. Selig, R. Saffrich, W. Ansorge, et al. Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis Blood, August 1, 2004; 104(3): 675 - 686. [Abstract] [Full Text] [PDF] U. Vijapurkar, N. Fischbach, W. Shen, C. Brandts, D. Stokoe, H. J. Lawrence, and C. Largman Protein Kinase C-Mediated Phosphorylation of the Leukemia-Associated HOXA9 Protein Impairs Its DNA Binding Ability and Induces Myeloid Differentiation Mol. Cell. Biol., May 1, 2004; 24(9): 3827 - 3837. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020