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>Revistas >Gaceta Médica de México >Año 2006, No. 2


Martínez-Mancilla M, Zafra-de la Rosa G, Reynoso-Gómez E, Astudillo-de la Vega H, Nambo-Lucio MJ, Benítez-Bribiesca L, Martínez-Avalos A, Rivera-Luna R, Gariglio P
La hemato-oncología molecular y las nuevas estrategias terapéuticas específicas en leucemia
Gac Med Mex 2006; 142 (2)

Idioma: Español
Referencias bibliográficas: 56
Paginas: 145-150
Archivo PDF: 493.04 Kb.


Texto completo




RESUMEN

En una elevada proporción de casos de leucemias de nuevo diagnóstico se detectan genes de fusión, los cuales frecuentemente presentan secuencias codificadoras de factores de transcripción. Se ha demostrado que algunas proteínas de fusión como Pml-Rara inhiben la diferenciación celular, al reclutar complejos correpresores nucleares que mantienen una actividad de histona desacetilasa (HDAC en inglés) sobre promotores de genes específicos importantes en diferenciación de una determinada estirpe celular. Esta represión transcripcional dependiente de HDAC representa una vía común en el desarrollo de leucemia y por lo tanto puede ser un blanco importante de nuevos compuestos terapéuticos. Por otro lado, la oncoproteína Bcr-Abl muestra una alta actividad de tirosina-cinasa, la cual desregula vías de transducción de señales involucradas normalmente en proliferación y apoptosis. Esta actividad aberrante puede ser afectada por inhibidores de transducción de señales (STIs, del inglés), los cuales bloquean la ruta oncogénica y representan un gran avance terapéutico.
En esta revisión analizamos con cierto detalle lo que se conoce en la actualidad sobre la represión transcripcional reversible controlada por HDAC y sobre la transducción de señales aumentada por Bcr-Abl. Adicionalmente indicamos que la aplicación de fármacos de bajo peso molecular para el control de las leucemias humanas, basada en el conocimiento de los mecanismos moleculares de la enfermedad, lleva a una remisión clínica, con bajo riesgo de efectos tóxicos secundarios, lo cual está aumentando la mejoría de una alta proporción de los enfermos.


Palabras clave: HDAC, factores de transcripción quiméricos, terapia molecular.


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>Revistas >Gaceta Médica de México >Año2006, No. 2
 

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