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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1897-1907. Prepublished online as a Blood First Edition Paper on November 21, 2006; DOI 10.1182/blood-2006-08-044156. This Article Full Text (PDF) Supplemental Methods and Tables All Versions of this Article: blood-2006-08-044156v1 109/5/1897    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 Kustikova, O. S. Articles by Baum, C. Search for Related Content PubMed PubMed Citation Articles by Kustikova, O. S. Articles by Baum, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 28, 2006 Accepted October 18, 2006 Retroviral vector insertion sites associated with dominant hematopoietic clones mark "stemness" pathways Olga S. Kustikova, Hartmut Geiger, Zhixiong Li, Martijn H. Brugman, Stuart M. Chambers, Chad A. Shaw, Karin Pike-Overzet, Dick de Ridder, Frank J.T. Staal, Gottfried von Keudell, Kerstin Cornils, Kalpana J. Nattamai, Ute Modlich, Gerard Wagemaker, Margaret A. Goodell, Boris Fehse, and Christopher Baum* Dept of Experimental Hematology, Hannover Medical School, Hannover, Germany Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States Dept of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands Center for Cell and Gene Therapy, Cell & Molecular Biology Program, Baylor College of Medicine, Houston, TX, United States Dept of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, United States Dept of Immunology, Erasmus Medical Center, Rotterdam, Netherlands Delft University of Technology, Delft, Netherlands Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany * Corresponding author; email: baum.christopher{at}mh-hannover.de. Evidence from model organisms and clinical trials reveals that the random insertion of retrovirus-based vectors in the genome of long-term repopulating hematopoietic cells may increase self-renewal or initiate malignant transformation. Clonal dominance of non-malignant cells is a particularly interesting phenotype as it may be caused by the dysregulation of genes that impact on self-renewal and competitive fitness. We have accumulated 280 retrovirus vector insertion sites (RVIS) from murine long-term studies resulting in benign or malignant clonal dominance. 22.5% of the RVIS are located in or near (up to 100 kb) to known proto-oncogenes, 49.6% in signaling genes, and 27.9% in other or unknown genes. The resulting insertional dominance database (IDDb) shows substantial overlaps with the transcriptome of hematopoietic stem/progenitor cells and the retrovirus-tagged cancer gene database (RTCGD). RVIS preferentially marked genes with high expression in hematopoietic stem/progenitor cells, and Gene Ontology revealed an overrepresentation of genes associated with cell cycle control, apoptosis signaling and transcriptional regulation, including major "stemness" pathways. The IDDb forms a powerful resource for the identification of genes that stimulate or transform hematopoietic stem/progenitor cells and is an important reference for vector biosafety studies in human gene therapy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Cattoglio, G. Facchini, D. Sartori, A. Antonelli, A. Miccio, B. Cassani, M. Schmidt, C. von Kalle, S. Howe, A. J. Thrasher, et al. Hot spots of retroviral integration in human CD34+ hematopoietic cells Blood, September 15, 2007; 110(6): 1770 - 1778. [Abstract] [Full Text] [PDF]

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