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- Title
Gene therapy: Is IL2RG oncogenic in T-cell development?
- Authors
Pike-Overzet, Karin; de Ridder, Dick; Weerkamp, Floor; Baert, Miranda R. M.; Verstegen, Monique M.; Brugman, Martijn H.; Howe, Steven J.; Reinders, Marcel J. T.; Thrasher, Adrian J.; Wagemaker, Gerard; van Dongen, Jacques J. M.; Staal, Frank J. T.
- Abstract
Arising from: N.-B. Woods, V. Bottero, M. Schmidt, C. von Kalle & I. M. Verma 440, 1123 (2006); see also communication from Thrasher et al.; Woods et al. replyThe gene IL2RG encodes the γ-chain of the interleukin-2 receptor and is mutated in patients with X-linked severe combined immune deficiency (X-SCID). Woods et al. report the development of thymus tumours in a mouse model of X-SCID after correction by lentiviral overexpression of IL2RG and claim that these were caused by IL2RG itself. Here we find that retroviral overexpression of IL2RG in human CD34+ cells has no effect on T-cell development, whereas overexpression of the T-cell acute lymphoblastic leukaemia (T-ALL) oncogene LMO2 leads to severe abnormalities. Retroviral expression of IL2RG may therefore not be directly oncogenic — rather, the restoration of normal signalling by the interleukin-7 receptor to X-SCID precursor cells allows progression of T-cell development to stages that are permissive for the pro-leukaemic effects of ectopic LMO2.
- Subjects
INTERLEUKIN-2; IMMUNODEFICIENCY; THYMUS; LYMPHOBLASTIC leukemia; T cells
- Publication
Nature, 2006, Vol 443, Issue 7109, pE5
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature05218