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This Article Full Text Full Text (PDF) 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 Fu, K.-L. Articles by Walsh, C. E. Search for Related Content PubMed PubMed Citation Articles by Fu, K.-L. Articles by Walsh, C. E. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RAPID COMMUNICATION Functional Correction of Fanconi Anemia Group A Hematopoietic Cells by Retroviral Gene Transfer Kai-Ling Fu, Jerome R. Lo Ten Foe, Hans Joenje, Kathleen W. Rao, Johnson M. Liu, and Christopher E. Walsh From the Gene Therapy Center and the Departments of Medicine, and Pathology and Pediatrics, University of North Carolina at Chapel Hill; the Chapel Hill, North Caroline 27599; Department of Human Genetics, Free University of Amsterdam, The Netherlands; and the National Institutes of Health, National Heart, Lung, and Blood Institute, Hematology Branch, Bethesda, MD. Fanconi anemia (FA) is an autosomal recessive genetic disorder characterized by a variety of physical anomalies, bone marrow failure, and an increased risk for malignancy. FA cells exhibit chromosomal instability and are hypersensitive to DNA cross-linking agents such as mitomycin C (MMC). FA is a clinically heterogeneous disorder and can be functionally divided into at least five different complementation groups (A-E). We previously described the use of a retroviral vector expressing the FAC cDNA in the complementation of mutant hematopoietic cells from FA-C patients. This vector is currently being tested in a clinical trial of ex vivo hematopoietic progenitor cell transduction. The FA-A group accounts for over 65% of all FA cases, and the FAA cDNA was recently identified by both expression and positional cloning techniques. We report here the transduction and phenotypic correction of lymphoblastoid cell lines from four unrelated FA-A patients, using two amphotropic FAA retroviral vectors. Expression of the FAA transgene was adequate to normalize cell growth, cell-cycle kinetics, and chromosomal breakage in the presence of MMC. We then analyzed the effect of retroviral vector transduction on hematopoietic progenitor cell growth. After FAA transduction of mutant progenitor cells, either colony number or colony size increased in the presence of MMC. In addition, FAA but not FAC retroviral transduction markedly improved colony growth of progenitor cells derived from an unclassified FA patient. FAA retroviral vectors should be useful for both complementation studies and clinical trials of gene transduction. Blood, Vol. 90 No. 9 (November 1), 1997: pp. 3296-3303 © 1997 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. A. Gush, K.-L. Fu, M. Grompe, and C. E. Walsh Phenotypic correction of Fanconi anemia group C knockout mice Blood, January 15, 2000; 95(2): 700 - 704. [Abstract] [Full Text] [PDF]

	Copyright © 1997 by American Society of Hematology         Online ISSN: 1528-0020