T-cell-directed TAL-1 expression induces T-cell malignancies in transgenic mice.
Cancer Res
; 56(22): 5113-9, 1996 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-8912842
ABSTRACT
The TAL-1 gene specifies for a basic domain-helix-loop-helix protein, which is involved in the control of normal hematopoiesis. In human pathology, the TAL-1 gene product is expressed in a high percentage of T-cell acute lymphoblastic leukemias in the pediatric age range; however, it has not been established whether the expression has a causal role in oncogenesis. In this report, we describe the phenotype of mouse transgenic lines obtained by inducing tal-1 protein expression in lymphoid tissues using the LCK promoter. The survival rate of tal-1 transgenic animals was much lower as compared with control mice. Histopathological analysis revealed lymphomas of T-cell type, often comprising a minor B-cell component. Some mice showed marked splenic lymphocyte depletion. Primary lymphocyte cultures showed partial independence from exogenous growth stimuli and increased resistance to low-serum apoptosis. To further unravel the tal-1 oncogenic potential, a strain of tal-1 transgenic mice was crossbred with p53-/- mice; the survival rate in these animals was reduced by more than one-half when compared with that of tal-1 mice, and histopathological analysis revealed exclusively T-cell lymphomas. These data indicate that TAL-1, expressed in T cells, is per se a potent oncogene, which may exert a key leukemogenetic role in the majority of T-cell acute lymphoblastic leukemias.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oncogenes
/
Fatores de Transcrição
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Linfócitos T
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Leucemia-Linfoma de Células T do Adulto
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Proteínas de Fusão Oncogênica
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Proteínas Proto-Oncogênicas
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Proteínas E2 de Adenovirus
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Proteínas de Ligação a DNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos