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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1929-1933. Prepublished online as a Blood First Edition Paper on October 30, 2003; DOI 10.1182/blood-2003-05-1624. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1624v1 103/5/1929    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 Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS A signaling mechanism for growth-related expression of fetal hemoglobin Natarajan V. Bhanu, Tiffany A. Trice, Y. Terry Lee, and Jeffery L. Miller From the Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. Increases in fetal hemoglobin have been identified after birth in several clinical settings associated with stressed or malignant erythropoiesis. To better understand the relationship between the expression of this fetal protein and growth, donated human erythroid progenitor cells were cultured in the presence of erythropoietin (EPO) plus the growth-modifying cytokine stem cell factor (SCF), and several growth-related signaling pathways were interrogated. Only the MEK1/2 inhibitor (PD98059) demonstrated significant effects on fetal hemoglobin. In the absence of PD98059, levels of fetal hemoglobin averaged 27.4% ± 7.9% in EPO+SCF compared with 1.26% ± 1.7% in EPO alone (P = .02). A linear dose response in levels of fetal hemoglobin to PD98059 was detected (0.16 µM = 27.13%, 0.8 µM = 19.6%, 4 µM = 12.2%, 20 µM = 1.54%). Western blot analyses revealed that SCF was required for phosphorylation of MEK and p44MAPK in this setting, and quantitative polymerase chain reaction demonstrated a significant increase in -globin mRNA. Particular perturbations of growth-related signaling may also function to activate tissue-specific genes normally expressed during fetal development. This concept may be relevant for the development of new treatment rationales for beta hemoglobinopathies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Uchida, K. N. Washington, J. Hayakawa, M. M. Hsieh, A. C. Bonifacino, A. E. Krouse, M. E. Metzger, R. E. Donahue, and J. F. Tisdale Development of a Human Immunodeficiency Virus Type 1-Based Lentiviral Vector That Allows Efficient Transduction of both Human and Rhesus Blood Cells J. Virol., October 1, 2009; 83(19): 9854 - 9862. [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] 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] A. N. Schechter Hemoglobin research and the origins of molecular medicine Blood, November 15, 2008; 112(10): 3927 - 3938. [Abstract] [Full Text] [PDF] M. Gabbianelli, O. Morsilli, A. Massa, L. Pasquini, P. Cianciulli, U. Testa, and C. Peschle Effective erythropoiesis and HbF reactivation induced by kit ligand in -thalassemia Blood, January 1, 2008; 111(1): 421 - 429. [Abstract] [Full Text] [PDF] M Wolk, J E Martin, and C Reinus Development of fetal haemoglobin-blood cells (F cells) within colorectal tumour tissues J. Clin. Pathol., June 1, 2006; 59(6): 598 - 602. [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] D. Rund and E. Rachmilewitz {beta}-Thalassemia N. Engl. J. Med., September 15, 2005; 353(11): 1135 - 1146. [Full Text] [PDF] S. P. Perrine Fetal Globin Induction--Can It Cure {beta} Thalassemia? Hematology, January 1, 2005; 2005(1): 38 - 44. [Abstract] [Full Text] [PDF] N. V. Bhanu, T. A. Trice, Y. T. Lee, N. M. Gantt, P. Oneal, J. D. Schwartz, P. Noel, and J. L. Miller A sustained and pancellular reversal of gamma-globin gene silencing in adult human erythroid precursor cells Blood, January 1, 2005; 105(1): 387 - 393. [Abstract] [Full Text] [PDF]

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