Is IL2RG oncogenic in T-cell development?

K Pike-Overzet, D de Ridder, F Weerkamp, MRM Baert, MM Verstegen, MH Brugman, SJ Howes, MJT Reinders, AJ Thrashers, G Wagemaker, JJM van Dongen, FJT Staal

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The gene IL2RG encodes the -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.
Original languageUndefined/Unknown
JournalNature: international weekly journal of science
Issue number7109
Publication statusPublished - 2006


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