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

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

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.

Publication types

  • Comment

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Transformation, Neoplastic*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genetic Therapy / adverse effects*
  • Humans
  • LIM Domain Proteins
  • Metalloproteins / genetics
  • Metalloproteins / metabolism
  • Mice
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology*

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LMO2 protein, human
  • Lmo2 protein, mouse
  • Metalloproteins
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-2