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|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|
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