AUTHOR=Pericole Fernando Vieira , Lazarini Mariana , de Paiva Luciana Bueno , Duarte Adriana da Silva Santos , Vieira Ferro Karla Priscila , Niemann Fernanda Soares , Roversi Fernanda Marconi , Olalla Saad Sara Teresinha TITLE=BRD4 Inhibition Enhances Azacitidine Efficacy in Acute Myeloid Leukemia and Myelodysplastic Syndromes JOURNAL=Frontiers in Oncology VOLUME=9 YEAR=2019 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00016 DOI=10.3389/fonc.2019.00016 ISSN=2234-943X ABSTRACT=
Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell-based disorders characterized by ineffective hematopoiesis, increased genomic instability and a tendency to progress toward acute myeloid leukemia (AML). MDS and AML cells present genetic and epigenetic abnormalities and, due to the heterogeneity of these molecular alterations, the current treatment options remain unsatisfactory. Hypomethylating agents (HMA), especially azacitidine, are the mainstay of treatment for high-risk MDS patients and HMA are used in treating elderly AML. The aim of this study was to investigate the potential role of the epigenetic reader bromodomain-containing protein-4 (BRD4) in MDS and AML patients. We identified the upregulation of the short variant BRD4 in MDS and AML patients, which was associated with a worse outcome of MDS. Furthermore, the inhibition of BRD4