Detección de mutaciones en el dominio tirosina quinasa de BCR-ABL1 en pacientes colombianos con leucemia mieloide crónica LMC, resistentes al imatinib

  • Gonzalo Vásquez Palacio Vásquez Palacio Universidad de Antioquia
  • Gloria Cecilia Ramírez Universidad de Antioquia
  • Carlos Enrique Muskus Universidad de Antioquia
  • José Domingo Torres Torres Hospital San Vicente de Paúl
  • Carlos Alberto Aya Universidad de Antioquia
Palabras clave: Leucemia mieloide crónica, Inhibidor de tirosina quinasa, Mutaciones en el dominio tirosina quinasa, Resistencia a imatinib, BCR-ABL1

Resumen

Introducción: Las mutaciones en el dominio BCR-ABL1, tirosina quinasa (TK) son mecanismos importantes de resistencia de los inhibidores de la tirosina quinasa (ITK) en pacientes con leucemia mieloide crónica (LMC).
Objetivo: Determinar el tipo y la frecuencia de las mutaciones en el dominio tirosina quinasa del gen BCR-ABL1, asociadas con falla en la respuesta al tratamiento con imatinib en pacientes con LMC y correlacionar el perfil de mutaciones con los hallazgos clínicos, demográficos, respuesta citogenética y respuesta molecular.
Materiales y métodos: Se realizó un estudio descriptivo de tipo prospectivo en pacientes con LMC en tratamiento con IMATINIB a quienes se les realizó cariotipo y análisis de mutaciones del dominio BCR-ABL1 mediante la técnica de PCR anidada.
Resultados: De los 23 pacientes estudiados en cuatro se encontraron mutaciones: dos presentaron la mutación E255K, uno presentó la mutación H396P y otro presentó doble mutación L387Ly T389P. Las mutaciones E255K que se ubican en la región P-loop y H396P en A-loop se asocian con mal pronóstico. La mutación T389P localizada en la región A-loop no está informada en algunas bases de datos.
Conclusiones: En este estudio encontramos cuatro mutaciones en el dominio tirosina quinasa (E255K, H396P, L387L y T389P) que podrían aportar información valiosa y guiar las decisiones de tratamiento. Es importante destacar que esta investigación de análisis mutacional del dominio BCR-ABL es la primera que se realiza en el país con la particularidad adicional de cubrir una población triétnica.

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Biografía del autor/a

Gonzalo Vásquez Palacio Vásquez Palacio, Universidad de Antioquia

Unidad de Genética Médica, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia

Gloria Cecilia Ramírez, Universidad de Antioquia

Unidad de Genética Médica, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia

Carlos Enrique Muskus, Universidad de Antioquia

Programa de Estudio y Control de Enfermedades Tropicales, PECET, Facultad de Medicina, Universidad de Antioquia, Medellín,
Colombia

José Domingo Torres Torres, Hospital San Vicente de Paúl

Departamento de Medicina Interna, Facultad de Medicina, Universidad de Antioquia, Hospital San Vicente de Paúl, Medellín,Colombia

Carlos Alberto Aya, Universidad de Antioquia

Unidad de Genética Médica, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia

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Publicado
2018-03-01
Cómo citar
[1]
Vásquez Palacio, G.V.P., Ramírez, G.C., Muskus, C.E., Torres, J.D.T. y Aya, C.A. 2018. Detección de mutaciones en el dominio tirosina quinasa de BCR-ABL1 en pacientes colombianos con leucemia mieloide crónica LMC, resistentes al imatinib. Revista Colombiana de Cancerología. 22, 1 (mar. 2018), 8-17. DOI:https://doi.org/10.35509/01239015.170.
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Artículos de investigación/originales