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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3848-3854. Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-04-1472. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1472v1 105/10/3848    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 Hu, R. Articles by Brodsky, R. A. Search for Related Content PubMed PubMed Citation Articles by Hu, R. Articles by Brodsky, R. A. Related Collections Hematopoiesis and Stem Cells Phagocytes Red Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS PIG-A mutations in normal hematopoiesis Rong Hu, Galina L. Mukhina, Steven Piantadosi, Jamie P. Barber, Richard J. Jones, and Robert A. Brodsky From the Johns Hopkins University, School of Medicine, Division of Hematology, Baltimore, MD, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. Paroxysmal nocturnal hemoglobinuria (PNH) is caused by phosphatidylinositol glycan–class A (PIG-A) mutations in hematopoietic stem cells (HSCs). PIG-A mutations have been found in granulocytes from most healthy individuals, suggesting that these spontaneous PIG-A mutations are important in the pathogenesis of PNH. It remains unclear if these PIG-A mutations have relevance to those found in PNH. We isolated CD34+ progenitors from 4 patients with PNH and 27 controls. The frequency of PIG-A mutant progenitors was determined by assaying for colony-forming cells (CFCs) in methylcellulose containing toxic doses of aerolysin (1 x 10-9 M). Glycosylphosphatidylinositol (GPI)–anchored proteins serve as receptors for aerolysin; thus, PNH cells are resistant to aerolysin. The frequency of aerolysin resistant CFC was 14.7 ± 4.0 x 10-6 in the bone marrow of healthy donors and was 57.0 ± 6.7 x 10-6 from mobilized peripheral blood. DNA was extracted from individual day-14 aerolysin-resistant CFCs and the PIG-A gene was sequenced to determine clonality. Aerolysin-resistant CFCs from patients with PNH exhibited clonal PIG-A mutations. In contrast, PIG-A mutations in the CFCs from controls were polyclonal, and did not involve T cells. Our data confirm the finding that PIG-A mutations are relatively common in normal hematopoiesis; however, the finding suggests that these mutations occur in differentiated progenitors rather than HSCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Is there a little PNH in all of us? Russell E. Ware Blood 2005 105: 3760-3761. [Full Text] [PDF] This article has been cited by other articles: R. A. Brodsky Narrative Review: Paroxysmal Nocturnal Hemoglobinuria: The Physiology of Complement-Related Hemolytic Anemia Ann Intern Med, April 15, 2008; 148(8): 587 - 595. [Full Text] [PDF] N. Inoue, T. Izui-Sarumaru, Y. Murakami, Y. Endo, J.-I. Nishimura, K. Kurokawa, M. Kuwayama, H. Shime, T. Machii, Y. Kanakura, et al. Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH) Blood, December 15, 2006; 108(13): 4232 - 4236. [Abstract] [Full Text] [PDF] D. J. Araten and L. Luzzatto The mutation rate in PIG-A is normal in patients with paroxysmal nocturnal hemoglobinuria (PNH) Blood, July 15, 2006; 108(2): 734 - 736. [Abstract] [Full Text] [PDF] R. A. Brodsky New Insights into Paroxysmal Nocturnal Hemoglobinuria Hematology, January 1, 2006; 2006(1): 24 - 28. [Abstract] [Full Text] [PDF]

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