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.
journal_name
Naturejournal_title
Natureauthors
Pike-Overzet K,de Ridder D,Weerkamp F,Baert MR,Verstegen MM,Brugman MH,Howe SJ,Reinders MJ,Thrasher AJ,Wagemaker G,van Dongen JJ,Staal FJdoi
10.1038/nature05218subject
Has Abstractpub_date
2006-09-21 00:00:00pages
E5; discussion E6-7issue
7109eissn
0028-0836issn
1476-4687pii
nature05218journal_volume
443pub_type
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