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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-03-0756. This Article Full Text (PDF) All Versions of this Article: 2002-03-0756v1 101/2/492    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 Wojda, U. Articles by Miller, J. L Search for Related Content PubMed PubMed Citation Articles by Wojda, U. Articles by Miller, J. L Social Bookmarking                   What's this? Submitted March 11, 2002 Accepted August 12, 2002 Fetal hemoglobin modulation during human erythropoiesis: stem cell factor has "late" effects related to the expression pattern of CD117 Urszula Wojda, Kristina R Leigh, Joyce M Njoroge, Kaedrea A Jackson, Bhanu V Natarajan, Michael L Stitely, and Jeffery L Miller* Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA Obstetrics and Gynecology, National Naval Medical Center, Bethesda, MD, USA * Corresponding author; email: jm7f{at}nih.gov. A cytokine screening assay of cultured peripheral blood cells obtained using immune rosetting and separation of progenitors was developed to identify determinants of fetal hemoglobin (HbF) modulation during adult erythropoiesis. Among the twelve erythroid growth-promoting cytokines tested, stem cell factor (SCF) at a concentration of 50 ng/mL resulted in the most significant increase in cell proliferation and HbF content. The average HbF:HbA ratio was 30.9 ± 18.7% in cultures containing SCF compared with 4.1 ± 2.2% in those grown with erythropoietin (EPO) alone (p value=8.5E-8). To further investigate the hemoglobin-modulating effects of SCF, we examined the surface expression pattern of the SCF receptor, CD117, among maturing erythroblasts. CD117 expression increased during the first week of culture and peaked on culture days 7-9. After culture day 9, the level of CD117 declined to lower levels. The rise in CD117 expression to high levels mirrored that of the transferrin receptor (CD71), and the subsequent reduction in CD117 was inversely related to increases in glycophorin A (GPA) expression. SCF related increases in the HbF:HbA ratio correlated with the expression pattern of CD117. SCF added during days 7-14 resulted in a more pancellular distribution of HbF on day 14 compared with the heterocellular distribution present in cultures supplemented with SCF on days 0-7. A significant SCF-mediated increase in HbF was also measured using cord blood derived progenitors. These results suggest that the HbF response to SCF is greatest at the late progenitor stage as a function of surface CD117 expression. 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. 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