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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3639-3645. Prepublished online as a Blood First Edition Paper on August 9, 2005; DOI 10.1182/blood-2005-04-1376. This Article Full Text (PDF) All Versions of this Article: 2005-04-1376v1 106/10/3639    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 Wu, C. J Articles by Ritz, J. Search for Related Content PubMed PubMed Citation Articles by Wu, C. J Articles by Ritz, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 4, 2005 Accepted July 22, 2005 Evidence for ineffective erythropoiesis in severe sickle cell disease Catherine J Wu*, Lakshamanan Krishnamurti, Jeffery L Kutok, Melinda Biernacki, Shelby Rogers, Wandi Zhang, Joseph H Antin, and Jerome Ritz Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Bone Marrow Transplant, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA; * Corresponding author; email: cwu{at}partners.org. Peripheral destruction of sickled erythrocytes is a cardinal feature of sickle cell disease (SCD). Less well established is the potential contribution of ineffective erythropoiesis to the pathophysiology of this hemoglobinopathy. Since patients with SCD frequently develop mixed hematopoietic chimerism after allogeneic nonmyeloablative stem cell transplantation, we used this opportunity to directly compare the differentiation and survival of SCD and donor-derived erythropoiesis in vivo. Donor and recipient erythropoiesis was compared in 4 patients with SCD and 4 without SCD who developed stable mixed hematopoietic chimerism following transplant. Molecular analysis of chimerism in peripheral blood and bone marrow demonstrated higher expression of donor-derived -globin RNA relative to the level of donor-derived genomic DNA in patients with SCD. Analysis of chimerism in immature (GYPA+, CD71hi) and mature (GYPA+, CD71neg) erythroblasts confirmed the intramedullary loss of SS erythroblasts with progressive maturation. In patients with SCD, relative enrichment of donor erythroid precursors began to appear at the onset of hemoglobinization. Ineffective erythropoiesis of homozygous SS progenitors thus provides a maturation advantage for AA or SA donor erythroid precursor cells that results in greater donor contribution to overall erythropoiesis following stem cell transplantation and improvement of clinical disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Bernaudin, G. Socie, M. Kuentz, S. Chevret, M. Duval, Y. Bertrand, J.-P. Vannier, K. Yakouben, I. Thuret, P. Bordigoni, et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease Blood, October 1, 2007; 110(7): 2749 - 2756. [Abstract] [Full Text] [PDF]

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