SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on October 17, 2002; DOI 10.1182/blood-2002-08-2617. This Article Full Text (PDF) All Versions of this Article: 2002-08-2617v1 101/5/2001    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 Witt, O. Articles by Pekrun, A. Search for Related Content PubMed PubMed Citation Articles by Witt, O. Articles by Pekrun, A. Social Bookmarking                   What's this? Submitted September 3, 2002 Accepted October 1, 2002 Induction of fetal hemoglobin expression by the histone-deacetylase inhibitor apicidin Olaf Witt*, Sven Moenkemeyer, Gabi Roenndahl, Bernhard Erdlenbruch, Dirk Reinhardt, Katrin Kanbach, and Arnulf Pekrun Children's Hospital, University of Goettingen, Goettingen, Germany Children's Hospital, Division of Hematology/Oncology, University of Muenster, Muenster, Germany * Corresponding author; email: owitt{at}gwdg.de. Pharmacologic stimulation of fetal hemoglobin (HbF) expression may be a promising approach for the treatment of ß-thalassemia. In this study, we have investigated the HbF-inducing activity and molecular mechanisms of specific histone-deacetylase (HDAC)-inhibitors in human K562 erythroleukemia cells. Apicidin was the most potent agent compared with other HDAC-inhibitors (Trichostatin A, MS-275, HC-Toxin, SAHA) and previously tested compounds (butyrate, phenylbutyrate, isobutyramide, hydroxyurea, 5-aza-cytidine), leading to a 10fold stimulation of HbF-expression at nano- to micromolar concentrations. Hyperacetylation of histones correlated with the ability of HDAC-inhibitors to stimulate HbF-synthesis. Furthermore, analysis of different MAP kinase signaling pathways revealed that p38 signaling was activated following apicidin-treatment of cells and inhibition of this pathway abolished the HbF-inducing effect of apicidin. Additionally, activation of the A-globin promoter by apicidin could be inhibited by p38-inhibitor SB203580. In summary, the novel HDAC-inhibitor apicidin was found to be a potent inducer of HbF-synthesis in K562 cells. The present data outline the role of histone-hyperacetylation and p38 MAP kinase signaling as molecular targets for pharmacological stimulation of HbF-production in erythroid cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Bhatia, J. L. Hallock, A. Dutta, S. Karkashon, L. S. Sterner, T. Miyazaki, A. Dean, and J. A. Little Short-chain fatty acid-mediated effects on erythropoiesis in primary definitive erythroid cells Blood, June 18, 2009; 113(25): 6440 - 6448. [Abstract] [Full Text] [PDF] T. H. Tezel, L. Geng, E. B. Lato, S. Schaal, Y. Liu, D. Dean, J. B. Klein, and H. J. Kaplan Synthesis and Secretion of Hemoglobin by Retinal Pigment Epithelium Invest. Ophthalmol. Vis. Sci., April 1, 2009; 50(4): 1911 - 1919. [Abstract] [Full Text] [PDF] I. Oehme, H. E. Deubzer, D. Wegener, D. Pickert, J.-P. Linke, B. Hero, A. Kopp-Schneider, F. Westermann, S. M. Ulrich, A. von Deimling, et al. Histone Deacetylase 8 in Neuroblastoma Tumorigenesis Clin. Cancer Res., January 1, 2009; 15(1): 91 - 99. [Abstract] [Full Text] [PDF] W. Aerbajinai, J. Zhu, Z. Gao, K. Chin, and G. P. Rodgers Thalidomide induces {gamma}-globin gene expression through increased reactive oxygen species mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis Blood, October 15, 2007; 110(8): 2864 - 2871. [Abstract] [Full Text] [PDF] J. Sangerman, M. S. Lee, X. Yao, E. Oteng, C.-H. Hsiao, W. Li, S. Zein, S. F. Ofori-Acquah, and B. S. Pace Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves {gamma}-globin activation by CREB1 and ATF-2 Blood, November 15, 2006; 108(10): 3590 - 3599. [Abstract] [Full Text] [PDF] A. Bank Regulation of human fetal hemoglobin: new players, new complexities Blood, January 15, 2006; 107(2): 435 - 443. [Abstract] [Full Text] [PDF] A. Mikhailov, M. Shinohara, and C. L. Rieder Topoisomerase II and histone deacetylase inhibitors delay the G2/M transition by triggering the p38 MAPK checkpoint pathway J. Cell Biol., August 16, 2004; 166(4): 517 - 526. [Abstract] [Full Text] [PDF] H. Cao, G. Stamatoyannopoulos, and M. Jung Induction of human {gamma} globin gene expression by histone deacetylase inhibitors Blood, January 15, 2004; 103(2): 701 - 709. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020