Please use this identifier to cite or link to this item: https://doi.org/10.3324/haematol.2013.093278
Title: The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors
Authors: Liss, A.
Ooi, C.-H.
Zjablovskaja, P.
Benoukraf, T. 
Radomska, H.S.
Ju, C.
Wu, M.
Balastik, M.
Delwel, R.
Brdicka, T.
Tan, P. 
Tenen, D.G.
Alberich-Jorda, M.
Issue Date: 2014
Citation: Liss, A., Ooi, C.-H., Zjablovskaja, P., Benoukraf, T., Radomska, H.S., Ju, C., Wu, M., Balastik, M., Delwel, R., Brdicka, T., Tan, P., Tenen, D.G., Alberich-Jorda, M. (2014). The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors. Haematologica 99 (4) : 697-705. ScholarBank@NUS Repository. https://doi.org/10.3324/haematol.2013.093278
Abstract: C/EPBα proteins, encoded by the CCAAT-enhancer-binding protein α 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/EBPα signature characterized by a set of genes up-regulated upon C/EBPα activation. We analyzed expression of the C/EBPα 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/EBPα dysfunctional subset. Remarkably, a large percentage of samples harboring C/EBPα biallelic mutations clustered within this subset. We hypothesize that re-activation of the C/EBPα signature in the C/EBPα dysfunctional subset could have therapeutic potential. In search for small molecules able to reverse the low expression of the C/EBPα signature we applied the connectivity map. This analysis predicted positive connectivity between the C/EBPα activation signature and histone deacetylase inhibitors. We showed that these inhibitors reactivate expression of the C/EBPα signature and promote granulocytic differentiation of primary samples from the C/EBPα dysfunctional subset harboring biallelic C/EBPα mutations. Altogether, our study identifies histone deacetylase inhibitors as potential candidates for the treatment of certain leukemias characterized by down-regulation of the C/EBPα signature. © Ferrata Storti Foundation.
Source Title: Haematologica
URI: http://scholarbank.nus.edu.sg/handle/10635/110312
ISSN: 15928721
DOI: 10.3324/haematol.2013.093278
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

9
checked on Jun 1, 2020

WEB OF SCIENCETM
Citations

9
checked on May 25, 2020

Page view(s)

67
checked on May 30, 2020

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.