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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2530-2533. Prepublished online as a Blood First Edition Paper on June 2, 2005; DOI 10.1182/blood-2005-03-1115. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-03-1115v1 106/7/2530    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 Calmels, B. Articles by Dunbar, C. E Search for Related Content PubMed PubMed Citation Articles by Calmels, B. Articles by Dunbar, C. E Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 18, 2005 Accepted May 23, 2005 Recurrent retroviral vector integration at the MDS1-EVI1 locus in non-human primate hematopoietic cells Boris Calmels, Cole Ferguson, Mikko O Laukkanen, Rima Adler, Marion Faulhaber, Hyeoung-Joon Kim, Stephanie Sellers, Peiman Hematti, Manfred Schmidt, Christof von Kalle, Keiko Akagi, Robert E Donahue, and Cynthia E Dunbar* Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA Chonnam National University Hospital, Gwangju, Korea, Republic of University of Freiburg, Freiburg, Germany University of Freiburg, Freiburg, Germany; Children's Hospital Research Foundation, Cincinnati, OH, USA Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA * Corresponding author; email: dunbarc{at}nhlbi.nih.gov. Recent reports linking insertional activiation of LMO2 following gene therapy for X-SCID have led to a re-evaluation of risks following gene therapy with retroviral vectors. In our analysis of 702 integration sites in rhesus macaques transplanted up to 7 years previously with autologous CD34+ cells transduced with amphotropic MLV-derived retroviral vectors containing marker genes, we detected insertion into one locus, the MDS1-EVI1 region, a total of 14 times in 9 animals. MDS1-EVI1 integrations were observed stably long-term, primarily in myeloid cells. We hypothesize that this over-representation likely results from an impact on the self-renewal and engraftment potential of CD34+ progenitor cells via insertional mutagenesis at this specific locus. There is no evidence of ongoing in vivo clonal expansion of the MDS1-EVI1 populations, and all animals are hematologically normal without evidence for leukemia. Characterization of integration sites in this relevant pre-clinical model provides critical information for gene therapy risk assessment as well as identification of genes controlling hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Cassani, E. Montini, G. Maruggi, A. Ambrosi, M. Mirolo, S. Selleri, E. Biral, I. Frugnoli, V. Hernandez-Trujillo, C. Di Serio, et al. Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy Blood, October 22, 2009; 114(17): 3546 - 3556. [Abstract] [Full Text] [PDF] Y.-J. Kim, Y.-S. Kim, A. Larochelle, G. Renaud, T. G. Wolfsberg, R. Adler, R. E. Donahue, P. Hematti, B.-K. Hong, J. Roayaei, et al. 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