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El mieloma múltiple (MM) es una neoplasia B post centro germinal caracterizada por la proliferación clonal de células plasmáticas en la médula ósea y la detección de una inmunoglobulina monoclonal en suero u orina, la proteína M. Se origina a partir de un proceso de transformación de múltiples pasos con acumulación progresiva de eventos genéticos que favorecen la proliferación y expansión del clon maligno. A nivel citogenético se observan anomalías primarias, directamente relacionadas con la patogénesis de la enfermedad, y secundarias, que incluyen ganancias y pérdidas de material genético, que aportan información de valor pronóstico adicional. Las anomalías primarias permiten dividir a los pacientes en dos grandes grupos: hiperdiploides, con ganancia de cromosomas, considerados de buen pronóstico, y no-hiperdiploides, con número modal variable, asociados a mala evolución clínica. Las anomalías secundarias incluyen: deleción 13q14/monosomía del cromosoma 13, deleción 17p13, alteraciones del cromosoma 1, específicamente ganancia/amplificación del brazo largo (1q21) y deleciones del brazo corto (1p), así como también rearreglos del gen MYC (8q24). Un nuevo subgrupo lo constituyen los MM doble hit que incluyen pacientes con: a) inactivación bialélica de TP53 (deleción en un alelo y mutación en el otro) y, b) estadio clínico ISS III con amplificación de 1q21 (≥4 copias), asociados a muy mal pronóstico. Una anomalía de reciente descripción es la inactivación bialélica del gen BCMA (B cell maturation antigen) (16p13.13), que constituye un mecanismo de recaída/resistencia al tratamiento anti-BCMA CAR T-cells, siendo importante su detección en pacientes pasibles de ser incorporados a estos esquemas terapéuticos. Sin duda, la profundización de la caracterización biológica del MM resulta de fundamental importancia en el marco de una medicina traslacional, contribuyendo a un mejor diagnóstico y/o pronóstico, y aportando información para nuevos abordajes terapéuticos.
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