title: Gene therapy: X-SCID transgene leukaemogenicity.
abstract: Gene therapy has been remarkably effective for the immunological reconstitution of patients with severe combined immune deficiency, but the occurrence of leukaemia in a few patients has stimulated debate about the safety of the procedure and the mechanisms of leukaemogenesis. Woods et al. forced high expression of the corrective therapeutic gene IL2RG, which encodes the gamma-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.
authors.affiliation: Molecular Immunology Unit, Institute of Child Health, University College London, London WC1N 1EH, UK. a.thrasher@ich.ucl.ac.uk
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
authors.forename: Christopher
authors.initials: C
authors.lastname: Baum
authors.forename: Ute
authors.initials: U
authors.lastname: Modlich
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsu
authors.forename: Brian
authors.initials: B
authors.lastname: Sorrentino
authors.forename: Linda
authors.initials: L
authors.lastname: Scobie
authors.forename: Ewan
authors.initials: E
authors.lastname: Cameron
authors.forename: Karen
authors.initials: K
authors.lastname: Blyth
authors.forename: Jim
authors.initials: J
authors.lastname: Neil
authors.forename: Salima Hacein-Bey
authors.initials: SH
authors.lastname: Abina
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects*; D006801:Humans; D007938:Leukemia / Q000209:etiology* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics* / Q000628:therapy*; D019076:Transgenes / Q000235:genetics*
chemical_list: D015513:Oncogene Proteins; D015375:Receptors, Interleukin-2