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2015, Número 1

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Rev Hematol Mex 2015; 16 (1)


Alteraciones genómicas y epigenómicas de las clonas de leucemia linfocítica crónica relacionadas con sus funciones básicas celulares

Valdespino-Gómez VM, Valdespino-Castillo PM

Idioma: Español
Referencias bibliográficas: 61
Paginas: 53-69
Archivo PDF: 546.03 Kb.


RESUMEN

La leucemia linfocítica crónica es el tipo de leucemia crónica más frecuente en la mayor parte de los países occidentales y, aunque se ha progresado significativamente en el estudio de su fisiopatología integral, su completo entendimiento aún es lejano. En esta revisión fragmentamos el análisis de las alteraciones genómicas y epigenómicas de las clonas de leucemia linfocítica crónica en dos grandes procesos, los correspondientes a las funciones básicas celulares (FBC) y a las funciones especializadas celulares de los linfocitos B transformados. Entre las principales alteraciones genómicas y epigenómicas de las funciones básicas celulares de las clonas de leucemia linfocítica crónica destacan: 1) la recurrencia de cuatro alteraciones en el número de copias de diferentes regiones cromosómicas, 2) la alteración de 20 de los genes conductores principales de su leucemogénesis, 3) perfiles epigenómicos predominantes de hipometilación de dinucleóticos CpG en muchos genes, enhancers y secuencias repetitivas, 4) la desregulación transcripcional por la expresión de una gran cantidad de transcritos alternativos, la sobreexpresión de transcritos de algunas vías metabólicas y la menor expresión de transcritos de las vías usadas en el procesamiento del ARN, así como del funcionamiento del proteosoma y ribosoma, y 5) la desregulación de ocho principales vías de señalización intracelulares. En la actualidad, muchas de estas diferentes alteraciones genómicas y epigenómicas que ocurren en las clonas de leucemia linfocítica crónica son motivo de intensa investigación traslacional, en busca de estrategias terapéuticas contra este tipo de leucemia.


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