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Fragile sites are preferential targets for integrations of MLV vectors in gene therapy

Gene Therapy volume 13, pages 1057–1059 (2006)Cite this article

A Corrigendum to this article was published on 22 January 2007

Abstract

Following gene therapy of SCID-X1 using murine leukemia virus (MLV) derived vector, two patients developed leukemia owing to an activating vector integration near the LMO2 gene. We found that these integrations reside within FRA11E, a common fragile site known to correlate with chromosomal breakpoints in tumors. Further analysis showed that fragile sites attract a nonrandom number of MLV integrations, shedding light on its integration mechanism and risk-to-benefit ratio in gene therapy.

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Acknowledgements

We thank Professor Norman Grover for his assistance in the statistical analyses, Dr Nicoletta Archidiacono for providing centromere 11 FISH probe and Professor Steve Scherer for providing chromosome 11 BAC clones.

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Authors and Affiliations

  1. Department of Genetics, Silberman Life Sciences Institute, Hebrew University, Jerusalem, Israel

    A C Bester, M Schwartz, N Ben-Porat & B Kerem

  2. Department of Internal Medicine I, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University, Freiburg, Germany

    M Schmidt & C Von Kalle

  3. INSERM Unit 429, Laboratoire de Cytogénétique, Paris, France

    A Garrigue, S Hacein-Bey-Abina, M Cavazzana-Calvo & A Fischer

  4. Department de Biotherapie Assistance Publique–Hopitaux de Paris, Paris, France

    S Hacein-Bey-Abina & M Cavazzana-Calvo

  5. Division of Experimental Hematology, Molecular and Gene Therapy Program, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH, USA

    C Von Kalle

  6. Unité d'Immunologie et d'Hématologie Pédiatriques, Hôpital Necker, Paris, France

    A Fischer

Authors
  1. A C Bester
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  2. M Schwartz
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  5. S Hacein-Bey-Abina
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  6. M Cavazzana-Calvo
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  7. N Ben-Porat
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  8. C Von Kalle
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  9. A Fischer
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  10. B Kerem
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Corresponding author

Correspondence to B Kerem.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Bester, A., Schwartz, M., Schmidt, M. et al. Fragile sites are preferential targets for integrations of MLV vectors in gene therapy. Gene Ther 13, 1057–1059 (2006). https://doi.org/10.1038/sj.gt.3302752

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  • DOI: https://doi.org/10.1038/sj.gt.3302752

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