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Mutaciones en los genes que regulan los procesos epigenéticos en la mastocitosis
Las anomalías en la regulación de los mecanismos epigenéticos de la expresión génica pueden influir significativamente en el desarrollo de la mastocitosis por medio de los siguientes fenómenos: expresión de micro-ARN específicos, pérdida de función de genes supresores, activación de oncogenes (tirosinas cinasas, proteínas de las vías de señalización), defectos de replicación y reparación del ADN, regulación de la apoptosis e inestabilidad del genoma.40-42 En los mastocitos con mutación del gen KIT se observa una expresión anómala de micro-ARN. Lee y cols. observaron una menor expresión de miR 539 y miR 381 en estas células. Estos micro-ARN participan en la inhibición de la expresión del MITF (microphthalmiaassociated transcription factor), que regula el desarrollo de los mastocitos y los melanocitos, así como la síntesis de triptasa y melanina (fig. 5).40-42
Los estudios con secuenciación multigénica sobre las neoplasias del sistema hematopoyético han revelado numerosas mutaciones que suelen producirse en la mastocitosis.43-47 Estas mutaciones afectan a los genes que regulan el proceso de formación del ARNm, la transmisión de señales y los mecanismos epigenéticos. Las mutaciones de los genes que participan en los mecanismos epigenéticos son frecuentes en las formas avanzadas de mastocitosis. Están ligadas a un pronóstico desfavorable y un menor tiempo de supervivencia. Por lo general, son las siguientes mutaciones: TET2 (desmetilación DNA), DNMT3A (metilación de islas CpG), ASXL1 (remodelación de la cromatina) y IDH2 (regulación de la metilación de histonas) (fig. 5).43-47
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