Paediatric patients with acute leukaemia and <i>KMT2A</i> (<i>MLL</i>) rearrangement show a distinctive expression pattern of histone deacetylases

Histone deacetylase inhibitors (HDACi) had emerged as promising drugs in leukaemia, but their toxicity due to lack of specificity limited their use. Therefore, there is a need to elucidate the role of HDACs in specific settings. The study of HDAC expression in childhood leukaemia could help to choos...

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Detalles Bibliográficos
Autores: Vega-García N, Malatesta R, Estella C, Pérez-Jaume S, Esperanza-Cebollada E, Torrebadell M, Català A, Gassiot S, Berrueco R, Ruiz-Llobet A, Alonso-Saladrigues A, Mesegué M, Pont-Martí S, Rives S, Camós M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p14647
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14647
Access Level:acceso abierto
Palabra clave:paediatric acute leukaemia
KMT2A (MLL)
histone deacetylases
HDAC inhibitors
epigenetics
Descripción
Sumario:Histone deacetylase inhibitors (HDACi) had emerged as promising drugs in leukaemia, but their toxicity due to lack of specificity limited their use. Therefore, there is a need to elucidate the role of HDACs in specific settings. The study of HDAC expression in childhood leukaemia could help to choose more specific HDACi for selected candidates in a personalized approach. We analysed HDAC1-11, SIRT1, SIRT7, MEF2C and MEF2D mRNA expression in 211 paediatric patients diagnosed with acute leukaemia. There was a global overexpression of HDACs, while specific HDACs correlated with clinical and biological features, and some even predicted outcome. Thus, some HDAC and MEF2C profiles probably reflected the lineage and the maturation of the blasts and some profiles identified specific oncogenic pathways active in the leukaemic cells. Specifically, we identified a distinctive signature for patients with KMT2A (MLL) rearrangement, with high HDAC9 and MEF2D expression, regardless of age, KMT2A partner and lineage. Moreover, we observed an adverse prognostic value of HDAC9 overexpression, regardless of KMT2A rearrangement. Our results provide useful knowledge on the complex picture of HDAC expression in childhood leukaemia and support the directed use of specific HDACi to selected paediatric patients with acute leukaemia.

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