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| rdf:type
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| 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. (en)
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| 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 (en)
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| 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 (en)
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| skos:notation
| - RIV/68378050:_____/14:00435104!RIV15-AV0-68378050
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - I, P(LK11213), P(LK21307)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/68378050:_____/14:00435104
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - C/EBPa; histone deacetylase inhibitor; acute myeloid leukemia (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
| - Haematologica-The Hematology Journal
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
| |
| http://linked.open...vavai/riv/projekt
| |
| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Brdička, Tomáš
- Balaštík, Martin
- Delwel, R.
- Radomska, H. S.
- Tenen, D. G.
- Alberich-Jorda, Meritxell
- Benoukraf, T.
- Wu, M. C.
- Ju, C.
- Liss, A.
- Ooi, C.
- Tan, P.
- Zjablovskaja, Polina
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| http://linked.open...ain/vavai/riv/wos
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| issn
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| number of pages
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| http://bibframe.org/vocab/doi
| - 10.3324/haematol.2013.093278
|
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