Proviral insertion indicates a dominant oncogenic role for Runx1/AML-1 in T-cell lymphoma.
Cancer Res
; 62(24): 7181-5, 2002 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-12499254
ABSTRACT
The RUNX1/AML1 gene is a frequent target for chromosomal translocations in human leukemia. The biological properties of the resulting fusion products and the finding that haploinsufficiency increases the risk of developing leukemia (W-J. Song et al., Nat. Genet., 23 166-175, 1999; M. Osata et al., Blood, 93 1817-1824, 1999) have led to the widely held view that RUNX1 loss-of-function is a key event. However, we now report that the gene is a target for insertional mutagenesis in T-cell lymphomas of mice carrying a MYC oncogene, where promoter insertion results in overexpression without affecting the integrity of the coding sequence. Moreover, Runx1 haploinsufficiency does not accelerate lymphoma development in MYC/Runx2 transgenic or murine leukemia virus-infected mice. These findings reveal that the Runx1 gene can also act as a dominant oncogene and suggest that the involvement of the Runx gene family in human leukemia may be more widespread and complex than previously realized.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Linfoma de Células T
/
Proteínas Proto-Oncogênicas
/
Provírus
/
Vírus da Leucemia Murina
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Proteínas de Ligação a DNA
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article