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Statements

Subject Item
n2:RIV%2F68378050%3A_____%2F14%3A00435104%21RIV15-AV0-68378050
rdf:type
skos:Concept n17:Vysledek
dcterms:description
C/EPB alpha proteins, encoded by the CCAAT-enhancer-binding protein a gene, play a crucial role in granulocytic development, and defects in this transcription factor have been reported in acute myeloid leukemia. Here, we defined the C/EPB alpha signature characterized by a set of genes up-regulated upon C/EPB alpha activation. We analyzed expression of the C/EPB alpha signature in a cohort of 525 patients with acute myeloid leukemia and identified a subset characterized by low expression of this signature. We referred to this group of patients as the C/EPB alpha dysfunctional subset. Remarkably, a large percentage of samples harboring C/EPB alpha biallelic mutations clustered within this subset. We hypothesize that re-activation of the C/EPB alpha signature in the C/EPB alpha dysfunctional subset could have therapeutic potential. In search for small molecules able to reverse the low expression of the C/EPB alpha signature we applied the connectivity map. This analysis predicted positive connectivity between the C/EPB alpha activation signature and histone deacetylase inhibitors. We showed that these inhibitors reactivate expression of the C/EPB alpha signature and promote granulocytic differentiation of primary samples from the C/EPB alpha dysfunctional subset harboring biallelic C/EPB alpha mutations. Altogether, our study identifies histone deacetylase inhibitors as potential candidates for the treatment of certain leukemias characterized by down-regulation of the C/EPB alpha signature. C/EPB alpha proteins, encoded by the CCAAT-enhancer-binding protein a gene, play a crucial role in granulocytic development, and defects in this transcription factor have been reported in acute myeloid leukemia. Here, we defined the C/EPB alpha signature characterized by a set of genes up-regulated upon C/EPB alpha activation. We analyzed expression of the C/EPB alpha signature in a cohort of 525 patients with acute myeloid leukemia and identified a subset characterized by low expression of this signature. We referred to this group of patients as the C/EPB alpha dysfunctional subset. Remarkably, a large percentage of samples harboring C/EPB alpha biallelic mutations clustered within this subset. We hypothesize that re-activation of the C/EPB alpha signature in the C/EPB alpha dysfunctional subset could have therapeutic potential. In search for small molecules able to reverse the low expression of the C/EPB alpha signature we applied the connectivity map. This analysis predicted positive connectivity between the C/EPB alpha activation signature and histone deacetylase inhibitors. We showed that these inhibitors reactivate expression of the C/EPB alpha signature and promote granulocytic differentiation of primary samples from the C/EPB alpha dysfunctional subset harboring biallelic C/EPB alpha mutations. Altogether, our study identifies histone deacetylase inhibitors as potential candidates for the treatment of certain leukemias characterized by down-regulation of the C/EPB alpha signature.
dcterms:title
The gene signature in CCAAT-enhancer-binding protein alpha dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors The gene signature in CCAAT-enhancer-binding protein alpha dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors
skos:prefLabel
The gene signature in CCAAT-enhancer-binding protein alpha dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors The gene signature in CCAAT-enhancer-binding protein alpha dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors
skos:notation
RIV/68378050:_____/14:00435104!RIV15-AV0-68378050
n3:aktivita
n10:I n10:P
n3:aktivity
I, P(LK11213), P(LK21307)
n3:cisloPeriodika
4
n3:dodaniDat
n4:2015
n3:domaciTvurceVysledku
n16:7171390 Zjablovskaja, Polina n16:8764611 Alberich-Jorda, Meritxell
n3:druhVysledku
n13:J
n3:duvernostUdaju
n6:S
n3:entitaPredkladatele
n12:predkladatel
n3:idSjednocenehoVysledku
18012
n3:idVysledku
RIV/68378050:_____/14:00435104
n3:jazykVysledku
n15:eng
n3:klicovaSlova
C/EBPa; histone deacetylase inhibitor; acute myeloid leukemia
n3:klicoveSlovo
n18:histone%20deacetylase%20inhibitor n18:C%2FEBPa n18:acute%20myeloid%20leukemia
n3:kodStatuVydavatele
IT - Italská republika
n3:kontrolniKodProRIV
[7EF6CD33A224]
n3:nazevZdroje
Haematologica-The Hematology Journal
n3:obor
n8:EB
n3:pocetDomacichTvurcuVysledku
4
n3:pocetTvurcuVysledku
13
n3:projekt
n14:LK21307 n14:LK11213
n3:rokUplatneniVysledku
n4:2014
n3:svazekPeriodika
99
n3:tvurceVysledku
Wu, M. C. Benoukraf, T. Tenen, D. G. Brdička, Tomáš Zjablovskaja, Polina Ju, C. Tan, P. Delwel, R. Alberich-Jorda, Meritxell Liss, A. Balaštík, Martin Radomska, H. S. Ooi, C.
n3:wos
000336256100021
s:issn
0390-6078
s:numberOfPages
9
n11:doi
10.3324/haematol.2013.093278