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Paediatric patients with acute leukaemia and KMT 2A ( MLL ) rearrangement show a distinctive expression pattern of histone deacetylases
Author(s) -
VegaGarcía Nerea,
Malatesta Roberta,
Estella Camino,
PérezJaume Sara,
EsperanzaCebollada Elena,
Torrebadell Montserrat,
Català Albert,
Gassiot Susanna,
Berrueco Rubén,
RuizLlobet Anna,
AlonsoSaladrigues Anna,
Mesegué Montserrat,
PontMartí Sandra,
Rives Susana,
Camós Mireia
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15436
Subject(s) - mef2c , cancer research , histone deacetylase , histone , biology , medicine , transcription factor , genetics , gene
Summary Histone deacetylase inhibitors ( HDAC i) 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 HDAC s in specific settings. The study of HDAC expression in childhood leukaemia could help to choose more specific HDAC i for selected candidates in a personalized approach. We analysed HDAC 1‐11 , SIRT 1, SIRT 7, MEF 2C and MEF 2D mRNA expression in 211 paediatric patients diagnosed with acute leukaemia. There was a global overexpression of HDAC s, while specific HDAC s correlated with clinical and biological features, and some even predicted outcome. Thus, some HDAC and MEF 2C 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 KMT 2A ( MLL ) rearrangement, with high HDAC 9 and MEF 2D expression, regardless of age, KMT 2A partner and lineage. Moreover, we observed an adverse prognostic value of HDAC 9 overexpression, regardless of KMT 2A rearrangement. Our results provide useful knowledge on the complex picture of HDAC expression in childhood leukaemia and support the directed use of specific HDAC i to selected paediatric patients with acute leukaemia.