| Evidence for ineffective erythropoiesis in severe sickle cell disease. | |
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MedLine Citation:
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PMID: 16091448 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 beta-globin RNA relative to the level of donor-derived genomic DNA in patients with SCD. Analysis of chimerism in immature (glycophorin A-positive [GYPA(+)], CD71(hi)) and mature (GYPA(+), CD71(neg)) 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 hemoglobin S (SS) progenitors thus provides a maturation advantage for homozygous hemoglobin A (AA) or heterozygous hemoglobin S/hemoglobin A (SA) donor erythroid precursor cells that results in greater donor contribution to overall erythropoiesis following stem-cell transplantation and improvement of clinical disease. |
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Authors:
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Catherine J Wu; Lakshamanan Krishnamurti; Jeffery L Kutok; Melinda Biernacki; Shelby Rogers; Wandi Zhang; Joseph H Antin; Jerome Ritz |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. Date: 2005-08-09 |
Journal Detail:
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Title: Blood Volume: 106 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-11-03 Completed Date: 2005-12-15 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 3639-45 Citation Subset: AIM; IM |
Affiliation:
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Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA. cwu@partners.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Anemia, Sickle Cell / metabolism*, pathology, therapy Antigens, CD / metabolism Cell Differentiation* Child Child, Preschool Erythroblasts / metabolism*, pathology Erythropoiesis* Female Glycophorin Hemolysis Humans Male Membrane Glycoproteins Middle Aged Receptors, Transferrin / metabolism Recovery of Function Sialoglycoproteins Stem Cell Transplantation* / methods Tissue Donors Transplantation Chimera / metabolism* Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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AI29530/AI/NIAID NIH HHS; HL070149/HL/NHLBI NIH HHS; K08 HL04293/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/CD71 antigen; 0/GYPA protein, human; 0/Glycophorin; 0/Membrane Glycoproteins; 0/Receptors, Transferrin; 0/Sialoglycoproteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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