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Blood, 1 January 2005, Vol. 105, No. 1, pp. 387-393. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2004-04-1599. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1599v1 105/1/387    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 Bhanu, N. V. Articles by Miller, J. L. Search for Related Content PubMed PubMed Citation Articles by Bhanu, N. V. Articles by Miller, J. L. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells Natarajan V. Bhanu, Tiffany A. Trice, Y. Terry Lee, Nicole M. Gantt, Patricia Oneal, Joseph D. Schwartz, Pierre Noel, and Jeffery L. Miller From the Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Hematology Services, Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD. We systematically compared cytokine-mediated increases or decreases in proliferation with globin gene and protein expression in adult human erythroblasts. Despite their opposite effects on growth, stem cell factor (SCF) and transforming growth factorbeta (TGF-B) had synergistic effects with respect to fetal hemoglobin (HbF): average HbF/HbF + adult hemoglobin (HbA) ratio in erythropoietin (EPO) = 1.4 ± 1.0%; EPO + TGF-B = 10.8 ± 1.9%; EPO + SCF = 19.1 ± 6.2%; and EPO + SCF + TGF-B (EST) = 39.3 ± 6.3%. Polymerase chain reaction (PCR) revealed significant increases in gamma-globin transcripts that were balanced by reduced beta-globin transcripts. Single-cell quantitative PCR demonstrated a complete reversal of gamma-globin gene silencing with detectable gamma-globin mRNA in more than 95% of the cells. Immunostaining with HbF antibodies also showed a pancellular distribution in EST (96.2 ± 0.01% HbF positive) compared with a heterocellular distribution in EPO (42.9 ± 0.01% HbF positive). As shown here for the first time, a robust and pancellular reversal of gamma-globin gene silencing among hemoglobinized erythroblasts from adult humans may be achieved in the absence of hereditary mutation or direct genomic manipulation. (Blood. 2005;105:387-393) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Sripichai, C. M. Kiefer, N. V. Bhanu, T. Tanno, S.-J. Noh, S.-H. Goh, J. E. Russell, C. L. Rognerud, C.-N. Ou, P. A. Oneal, et al. Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming Blood, September 10, 2009; 114(11): 2299 - 2306. [Abstract] [Full Text] [PDF] W. Aerbajinai, J. Zhu, C. Kumkhaek, K. Chin, and G. P. Rodgers SCF induces {gamma}-globin gene expression by regulating downstream transcription factor COUP-TFII Blood, July 2, 2009; 114(1): 187 - 194. [Abstract] [Full Text] [PDF] R. Mabaera, M. R. Greene, C. A. Richardson, S. J. Conine, C. D. Kozul, and C. H. Lowrey Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin Blood, January 1, 2008; 111(1): 411 - 420. [Abstract] [Full Text] [PDF] M. M. Hsieh, N. S. Linde, A. Wynter, M. Metzger, C. Wong, I. Langsetmo, A. Lin, R. Smith, G. P. Rodgers, R. E. Donahue, et al. HIF prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques Blood, September 15, 2007; 110(6): 2140 - 2147. [Abstract] [Full Text] [PDF] I. Amoyal, E. Prus, and E. Fibach Vanadate Elevates Fetal Hemoglobin in Human Erythroid Precursors by Inhibiting Cell Maturation Experimental Biology and Medicine, May 1, 2007; 232(5): 654 - 661. [Abstract] [Full Text] [PDF] P. A. Oneal, N. M. Gantt, J. D. Schwartz, N. V. Bhanu, Y. T. Lee, J. W. Moroney, C. H. Reed, A. N. Schechter, N. L. C. Luban, and J. L. Miller Fetal hemoglobin silencing in humans Blood, September 15, 2006; 108(6): 2081 - 2086. [Abstract] [Full Text] [PDF] J. Jiang, S. Best, S. Menzel, N. Silver, M. I. Lai, G. L. Surdulescu, T. D. Spector, and S. L. Thein cMYB is involved in the regulation of fetal hemoglobin production in adults Blood, August 1, 2006; 108(3): 1077 - 1083. [Abstract] [Full Text] [PDF] N. V. Bhanu, Y. T. Lee, P. A. Oneal, C. L. Rognerud, C.-N. Ou, and J. L. Miller Silencing Reversed: Coordinated Expression of Embryonic and Fetal Globin Genes in Adult Human Erythroblasts. Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 821 - 821. [Abstract]

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