Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 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
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Tables
Right arrow All Versions of this Article:
blood-2007-01-068759v1
110/6/1770    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cattoglio, C.
Right arrow Articles by Mavilio, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cattoglio, C.
Right arrow Articles by Mavilio, F.
Related Collections
Right arrow Hematopoiesis and Stem Cells
Right arrow Neoplasia
Right arrow Oncogenes and Tumor Suppressors
Right arrow Free Research Articles
Right arrow Gene Therapy
Right arrowRelated Article in Blood Online
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article in Blood Online:

RIS defines risk
Utpal P. Davé
Blood 2007 110: 1704. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 BloodHome page
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.
Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector-transduced CD34+ cells
Blood, May 28, 2009; 113(22): 5434 - 5443.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. Laje, D. Shang, W. Cao, M. Niiya, M. Endo, A. Radu, N. DeRogatis, F. Scheiflinger, P. W. Zoltick, A. W. Flake, et al.
Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell-mediated gene therapy
Blood, March 5, 2009; 113(10): 2172 - 2180.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
G. P. Wang, A. Garrigue, A. Ciuffi, K. Ronen, J. Leipzig, C. Berry, C. Lagresle-Peyrou, F. Benjelloun, S. Hacein-Bey-Abina, A. Fischer, et al.
DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer
Nucleic Acids Res., May 1, 2008; 36(9): e49 - e49.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020