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Idioma: Español
Referencias bibliográficas: 84
Paginas: 162-174
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RESUMEN

El gen FMS-like tyrosine kinase 3 (FLT3) codifica para un receptor indispensable en el desarrollo, proliferación y supervivencia de las células hematopoyéticas. Este artículo describe las características biológicas del gen, el funcionamiento normal y patológico de la proteína y las principales mutaciones de interés en la práctica médica. El FLT3 se localiza en el cromosoma 13 y está constituido por 24 exones. La síntesis de la proteína y la activación posterior dependen de diferentes procesos celulares y del FLT3 ligando. Entre las alteraciones más importantes del gen destacan por su frecuencia e implicación en el pronóstico de las enfermedades, la duplicación interna en tándem en la región codificante del dominio yuxtamembrana (FLT3-ITD) y las mutaciones puntuales en el dominio tirosina cinasa (FLT3-TKD). Estas mutaciones son de especial interés para la toma de decisiones terapéuticas en la leucemia mieloide aguda. La alteración FLT3-ITD está descrita hasta en un 25% de los pacientes con leucemia mieloide aguda y constituye un predictor independiente de mal pronóstico y mayor riesgo de recaída. El cociente alélico (AR) FLT3-ITD, que refleja la carga leucémica, tiene un papel significativo, donde el AR ‹ 0.5 o ≥ 0.5 define categorías de pronóstico. En lo referente a los esquemas terapéuticos, los ensayos clínicos con inhibidores de la proteína FLT3, dirigidos a las mutaciones FLT3-ITD y a las FLT3-TKD, han abierto una puerta a la medicina de precisión en la leucemia mieloide aguda; sin embargo, aún quedan obstáculos por superar, como la toxicidad, especificidad y la resistencia en el paciente.

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