Paediatric patients with acute leukaemia and KMT2A (MLL) rearrangement show a distinctive expression pattern of histone deacetylases
Por:
Vega-García N, Malatesta R, Estella-Aguado MC, Pérez-Jaume S, Esperanza-Cebollada E, Torrebadell-Burriel M, Català-Temprano A, Gassiot S, Berrueco R, Ruiz-Llobet A, Alonso-Saladrigues A, Mesegue-Meda M, Pont-Martí S, Rives-Solà S and Camós-Guijosa M
Publicada:
1 ago 2018
Ahead of Print:
5 jul 2018
Categoría:
Hematology
Resumen:
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.
Filiaciones:
Vega-García N:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Malatesta R:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Estella-Aguado MC:
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Pérez-Jaume S:
Developmental Tumor Biology Laboratory, Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Esperanza-Cebollada E:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Torrebadell-Burriel M:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Català-Temprano A:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Paediatric Haematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Gassiot S:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Berrueco R:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Paediatric Haematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Ruiz-Llobet A:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Paediatric Haematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Alonso-Saladrigues A:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Paediatric Haematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Mesegue-Meda M:
Paediatric Haematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Pont-Martí S:
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Rives-Solà S:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
Paediatric Haematology and Oncology Department, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Camós-Guijosa M:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
Haematology Laboratory, Hospital Sant Joan de Déu Barcelona, University of Barcelona, Barcelona, Spain
Institut de Recerca Hospital Sant Joan de Déu Barcelona, Barcelona, Spain
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