Please use this identifier to cite or link to this item:
https://doi.org/10.3324/haematol.2013.093278
DC Field | Value | |
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dc.title | The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors | |
dc.contributor.author | Liss, A. | |
dc.contributor.author | Ooi, C.-H. | |
dc.contributor.author | Zjablovskaja, P. | |
dc.contributor.author | Benoukraf, T. | |
dc.contributor.author | Radomska, H.S. | |
dc.contributor.author | Ju, C. | |
dc.contributor.author | Wu, M. | |
dc.contributor.author | Balastik, M. | |
dc.contributor.author | Delwel, R. | |
dc.contributor.author | Brdicka, T. | |
dc.contributor.author | Tan, P. | |
dc.contributor.author | Tenen, D.G. | |
dc.contributor.author | Alberich-Jorda, M. | |
dc.date.accessioned | 2014-11-26T08:30:57Z | |
dc.date.available | 2014-11-26T08:30:57Z | |
dc.date.issued | 2014 | |
dc.identifier.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 | |
dc.identifier.issn | 15928721 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/110312 | |
dc.description.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. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.3324/haematol.2013.093278 | |
dc.source | Scopus | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.contributor.department | DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE | |
dc.description.doi | 10.3324/haematol.2013.093278 | |
dc.description.sourcetitle | Haematologica | |
dc.description.volume | 99 | |
dc.description.issue | 4 | |
dc.description.page | 697-705 | |
dc.description.coden | HAEMA | |
dc.identifier.isiut | 000336256100021 | |
Appears in Collections: | Staff Publications |
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