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Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-03-0712. This Article Full Text (PDF) All Versions of this Article: 2003-03-0712v1 102/13/4582    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 Kean, L. S Articles by Archer, D. R Search for Related Content PubMed PubMed Citation Articles by Kean, L. S Articles by Archer, D. R Social Bookmarking                   What's this? Submitted March 6, 2003 Accepted August 10, 2003 Chimerism and cure: hematologic and pathologic correction of murine sickle cell disease Leslie S Kean, Elizabeth A Manci, Jennifer Perry, Can Balkan, Shana Coley, David Holtzclaw, Andrew B Adams, Christian P Larsen, Lewis L Hsu, and David R Archer* Department of Pediatrics, Emory University, Atlanta, GA, USA Department of Pathology, University of South Alabama, Mobile, AL, USA Department of Pediatrics, Ege University, Izmir, Turkey Department of Surgery, Emory University, Atlanta, GA, USA * Corresponding author; email: darcher{at}emory.edu. Bone marrow transplantation (BMT) is the only curative therapy for sickle cell disease (SCD). However, the morbidity and mortality related to pretransplant myeloablative chemotherapy often outweighs the morbidity of SCD itself, thus severely limiting the number of patients eligible for transplant. While nonmyeloablative transplantation is expected to reduce the risk of BMT, it will likely result in mixed-chimerism rather than complete replacement with donor stem cells. Clinical application of nonmyeloablative transplantation thus requires knowledge of the effect of mixed-chimerism on SCD pathophysiology. We have therefore created a panel of transplanted SCD mice displaying an array of RBC and WBC chimerism. A significant enrichment of RBC over WBC chimerism occurred in these mice, due to the dramatic survival advantage of donor over sickle RBC in the peripheral blood. Increasing levels of RBC chimerism provided progressive correction of hematologic and pathologic abnormalities. However, sickle bone marrow and splenic hematopoiesis was not corrected until peripheral blood sickle RBC were fully replaced with normal RBC. These results have important and unexpected implications for non-myeloablative BMT for SCD. As the critical hematopoietic organs were not corrected without full RBC replacement, 100% peripheral blood RBC chimerism becomes the most important benchmark for cure after nonmyeloablative BMT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Perumbeti, T. Higashimoto, F. Urbinati, R. Franco, H. J. Meiselman, D. Witte, and P. Malik A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction Blood, August 6, 2009; 114(6): 1174 - 1185. [Abstract] [Full Text] [PDF] D. Lisini, M. Zecca, G. Giorgiani, D. Montagna, R. Cristantielli, M. Labirio, P. Grignani, C. Previdere, A. Di Cesare-Merlone, G. Amendola, et al. 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