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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2699-2706. Prepublished online as a Blood First Edition Paper on December 7, 2004; DOI 10.1182/blood-2004-07-2648. This Article Full Text (PDF) All Versions of this Article: 2004-07-2648v1 105/7/2699    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 Schmidt, M. Articles by von Kalle, C. Search for Related Content PubMed PubMed Citation Articles by Schmidt, M. Articles by von Kalle, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 13, 2004 Accepted November 26, 2004 Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial Manfred Schmidt, Salima Hacein-Bey-Abina, Manuela Wissler, Frederique Carlier, Annick Lim, Claudia Prinz, Hanno Glimm, Isabelle Andre-Schmutz, Christophe Hue, Alexandrine Garrigue, Francoise Le Deist, Chantal Lagresle, Alain Fischer, Marina Cavazzana-Calvo*, and Christof von Kalle Department of Internal Medicine, University of Freiburg, Freiburg, Germany Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany Inserm Unit 429, Hopital Necker, Paris Cedex, France; Department of Biotherapy AP-HP, Hopital Necker, Paris Cedex, France Unite de Biologie Moleculaire du Gene, Inserm Unit 277, Institut Pasteur, Paris Cedex, France Laboratoire d'Immunologie Pediatrique AP-HP, Hopital Necker, Paris Cedex, France Unite d'Immunologie et d'Hematologie Pediatriques, Hopital Necker, Paris Cedex, France Department of Experimental Hematology, Children's Hospital Research Foundation, Cincinnati, OH, USA * Corresponding author; email: m.cavazzana{at}nck.ap-hop-paris.fr. Immune function has been restored in 9 out of 10 children with X-linked severe combined immunodeficiency by c gene transfer in CD34+ cells. The distribution of both TCR V family usage and TCR V CDR3 length revealed a broadly diversified T cell repertoire. Retroviral integration site analysis in T cells demonstrated a high number of distinct insertion sites, indicating polyclonality of genetically corrected cell clones, in all patients. Detection of c transgene expression on patients' mature myeloid cells has prompted us to investigate the nature of the most immature transduced hematopoietic precursor cells. Insertion sites shared by T and B lymphocytes as well as highly purified granulocytes and monocytes demonstrate the correction of common multipotent progenitor cells. Moreover, our data show that differentiated leukocytes share the same exact insertion sites with CD34+ cells which we obtained 8 months later and that were able to generate long-term culture-initiating cells (LTC-IC). This finding demonstrates the initial transduction of very primitive multipotent progenitor cells with self-renewal capacity. These results provide a first evidence in the setting of a clinical trial that CD34+ cells maintain both lymphomyeloid potential as well as self-renewal capacity after ex-vivo manipulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. B. Gaspar, A. Aiuti, F. Porta, F. Candotti, M. S. Hershfield, and L. D. Notarangelo How I treat ADA deficiency Blood, October 22, 2009; 114(17): 3524 - 3532. [Abstract] [Full Text] [PDF] S. Amorosi, I. Russo, G. Amodio, C. Garbi, L. Vitiello, L. Palamaro, M. Adriani, I. Vigliano, and C. Pignata The Cellular Amount of the Common {gamma}-Chain Influences Spontaneous or Induced Cell Proliferation J. Immunol., March 1, 2009; 182(5): 3304 - 3309. [Abstract] [Full Text] [PDF] J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. 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