Is IL2RG oncogenic in T-cell development?

Karin Pike-Overzet, 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 and Frank J. T. Staal ()
Additional contact information
Karin Pike-Overzet: Erasmus University Medical Center
Dick de Ridder: Information and Communication Theory Group, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology
Floor Weerkamp: Erasmus University Medical Center
Miranda R. M. Baert: Erasmus University Medical Center
Monique M. Verstegen: Erasmus University Medical Center
Martijn H. Brugman: Erasmus University Medical Center
Steven J. Howe: Information and Communication Theory Group, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology
Marcel J. T. Reinders: Erasmus University Medical Center
Adrian J. Thrasher: Molecular Immunology Unit, Institute of Child Health, University College London
Gerard Wagemaker: Erasmus University Medical Center
Jacques J. M. van Dongen: Erasmus University Medical Center
Frank J. T. Staal: Erasmus University Medical Center

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

Abstract: Abstract Arising from: N.-B. Woods, V. Bottero, M. Schmidt, C. von Kalle & I. M. Verma Nature 440, 1123 (2006); see also communication from Thrasher et al. ; Woods et al. reply The 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.1 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.

Date: 2006
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DOI: 10.1038/nature05218

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