Please use this identifier to cite or link to this item:
|Title:||The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors||Authors:||Liss, A.
|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.
checked on Jul 29, 2021
WEB OF SCIENCETM
checked on Jul 29, 2021
checked on Aug 1, 2021
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.