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Comment
. 2006 Sep 21;443(7109):E5; discussion E6-7.
doi: 10.1038/nature05218.

Gene therapy: is IL2RG oncogenic in T-cell development?

Karin Pike-Overzet  1 , Dick de Ridder, Floor Weerkamp, Miranda R M Baert, Monique M Verstegen, Martijn H Brugman, Steven J Howe, Marcel J T Reinders, Adrian J Thrasher, Gerard Wagemaker, Jacques J M van Dongen, Frank J T Staal
Affiliations
Comment

Gene therapy: is IL2RG oncogenic in T-cell development?

Karin Pike-Overzet et al. Nature. .

Abstract

The gene IL2RG encodes the gamma-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.

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