@article{Adam Liss_Chia-Huey Ooi_Polina Zjablovskaja_Touati Benoukraf_Hanna S. Radomska_Chen Ju_Mengchu Wu_Martin Balastik_Ruud Delwel_Tomas Brdicka_Patrick Tan_Daniel G. Tenen_Meritxell Alberich-Jorda_2014, place={Pavia, Italy}, title={The gene signature in CCAAT-enhancer-binding protein α dysfunctional acute myeloid leukemia predicts responsiveness to histone deacetylase inhibitors}, volume={99}, url={https://haematologica.org/article/view/7000}, DOI={10.3324/haematol.2013.093278}, abstractNote={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.}, number={4}, journal={Haematologica}, author={Adam Liss and Chia-Huey Ooi and Polina Zjablovskaja and Touati Benoukraf and Hanna S. Radomska and Chen Ju and Mengchu Wu and Martin Balastik and Ruud Delwel and Tomas Brdicka and Patrick Tan and Daniel G. Tenen and Meritxell Alberich-Jorda}, year={2014}, month={Mar.}, pages={697-705} }