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Inversión de la apoptosis por el factor de transcripción quimérico E2A-HLF asociado a la leucemia
T Inaba1, T Inukai, T Yoshihara
1Department of Experimental Oncology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nature
|August 8, 1996
Resumen
El gen de fusión E2A-HLF promueve la leucemia al afectar la supervivencia celular. Esta proteína oncogénica inhibe la apoptosis, lo que sugiere un papel en el bloqueo de las vías de muerte celular conservadas durante la leucemogénesis.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- El gen de fusión E2A-HLF, resultante de la translocación cromosómica t(17;19), está implicado en la transformación leucémica de los precursores tempranos de las células B.
- El mecanismo preciso por el cual E2A-HLF impulsa la leucemogénesis sigue siendo en gran medida desconocido.
Objetivo del estudio:
- Para aclarar el mecanismo de la transformación leucémica impulsada por el gen de fusión E2A-HLF.
- Para investigar el papel de E2A-HLF en la supervivencia celular y la apoptosis.
Principales métodos:
- Utilizó supresores dominantes negativos para inhibir la actividad E2A-HLF en las células de leucemia humana.
- Introdujo la proteína de fusión E2A-HLF en linfocitos pro-B murinos para evaluar sus efectos sobre la apoptosis.
Principales resultados:
- Las células de leucemia humana que expresan un supresor E2A-HLF dominante negativo se sometieron a una apoptosis rápida, lo que sugiere que E2A-HLF afecta principalmente la supervivencia celular.
- E2A-HLF revirtió tanto la apoptosis dependiente de la interleucina-3 como la mediada por la p53 en los linfocitos pro-B murinos.
Conclusiones:
- La oncoproteína E2A-HLF probablemente promueve la leucemia al inhibir las vías de muerte celular, mejorando así la supervivencia celular.
- La homología estructural entre el dominio de unión al ADN de E2A-HLF y las proteínas de muerte celular de Caenorhabditis elegans sugiere un mecanismo conservado en la leucemogénesis.
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