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Is IL2RG oncogenic in T-cell development?

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 , 2006. "Is IL2RG oncogenic in T-cell development?," Nature, Nature, vol. 443(7109), pages 5-5, September.
    • Handle: RePEc:nat:nature:v:443:y:2006:i:7109:d:10.1038_nature05218
    DOI: 10.1038/nature05218
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