X-SCID transgene leukaemogenicity

Adrian J. Thrasher (), H. Bobby Gaspar, Christopher Baum, Ute Modlich, Axel Schambach, Fabio Candotti, Makoto Otsu, Brian Sorrentino, Linda Scobie, Ewan Cameron, Karen Blyth, Jim Neil, Salima Hacein-Bey Abina, Marina Cavazzana-Calvo and Alain Fischer
Additional contact information
Adrian J. Thrasher: Molecular Immunology Unit, Institute of Child Health, University College London
H. Bobby Gaspar: Molecular Immunology Unit, Institute of Child Health, University College London
Christopher Baum: Hannover Medical School
Ute Modlich: Hannover Medical School
Axel Schambach: Hannover Medical School
Fabio Candotti: Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health
Makoto Otsu: Center for Experimental Medicine, University of Tokyo
Brian Sorrentino: St Jude Children's Research Hospital
Linda Scobie: Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow
Ewan Cameron: Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow
Karen Blyth: Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow
Jim Neil: Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow
Salima Hacein-Bey Abina: INSERM Unit 768, Hôpital Necker, Assistance Publique–Hôpitaux de Paris
Marina Cavazzana-Calvo: INSERM Unit 768, Hôpital Necker, Assistance Publique–Hôpitaux de Paris
Alain Fischer: INSERM Unit 768, Hôpital Necker, Assistance Publique–Hôpitaux de Paris

Nature, 2006, vol. 443, issue 7109, E5-E6

Abstract: Abstract Arising from: Woods, N.-B., Bottero, V., Schmidt, M., von Kalle, C. & Verma, I. M. Nature 440, 1123 (2006); see also communication from Pike-Overzet et al. ; Woods et al. reply Gene therapy has been remarkably effective for the immunological reconstitution of patients with severe combined immune deficiency1,2,3, but the occurrence of leukaemia in a few patients has stimulated debate about the safety of the procedure and the mechanisms of leukaemogenesis4. Woods et al.5 forced high expression of the corrective therapeutic gene IL2RG, which encodes the γ-chain of the interleukin-2 receptor, in a mouse model of the disease and found that tumours appeared in a proportion of cases. Here we show that transgenic IL2RG does not necessarily have potent intrinsic oncogenic properties, and argue that the interpretation of this observation with respect to human trials is overstated.

Date: 2006
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DOI: 10.1038/nature05219

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