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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1770-1778. Prepublished online as a Blood First Edition Paper on May 16, 2007; DOI 10.1182/blood-2007-01-068759. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: blood-2007-01-068759v1 110/6/1770    most recent 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 Cattoglio, C. Articles by Mavilio, F. Search for Related Content PubMed PubMed Citation Articles by Cattoglio, C. Articles by Mavilio, F. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Free Research Articles Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Hot spots of retroviral integration in human CD34+ hematopoietic cells Claudia Cattoglio1, Giulia Facchini2, Daniela Sartori1, Antonella Antonelli3, Annarita Miccio3, Barbara Cassani3, Manfred Schmidt4, Christof von Kalle4, Steve Howe5, Adrian J. Thrasher5, Alessandro Aiuti3, Giuliana Ferrari3,6, Alessandra Recchia2, and Fulvio Mavilio2 1 Italian Institute of Technology, Unit of Molecular Neuroscience, Istituto Scientifico H. San Raffaele, Milan, Italy; 2 Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy; 3 San Raffaele Telethon Institute for Gene Therapy, Milan, Italy; 4 National Center for Tumor Diseases, Heidelberg, Germany; 5 Molecular Immunology Unit, Institute of Child Health, London, United Kingdom; 6 Vita-Salute San Raffaele University, Milan, Italy Insertional oncogenesis is a possible consequence of the integration of gamma-retroviral (RV) or lentiviral (LV) vectors into the human genome. RV common insertion sites (CISs) have been identified in hematopoietic malignancies and in the nonmalignant progeny of transduced hematopoietic stem/progenitor cells (HSCs), possibly as a consequence of clonal selection in vivo. We have mapped a large number of RV and LV integrations in human CD34+ HSCs, transduced in vitro and analyzed without selection. Recurrent insertion sites (hot spots) account for more than 21% of the RV integration events, while they are significantly less frequent in the case of LV vectors. RV but not LV hot spots are highly enriched in proto-oncogenes, cancer-associated CISs, and growth-controlling genes, indicating that at least part of the biases observed in the HSC progeny in vivo are characteristics of RV integration, already present in nontransplanted cells. Genes involved in hematopoietic and immune system development are targeted at high frequency and enriched in hot spots, suggesting that the CD34+ gene expression program is instrumental in directing RV integration. The lower propensity of LV vectors for integrating in potentially dangerous regions of the human genome may be a factor determining a better safety profile for gene therapy applications. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: RIS defines risk Utpal P. 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