C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis
dc.contributor.author | Collins, Cailin | |
dc.contributor.author | Wang, Jingya | |
dc.contributor.author | Miao, Hongzhi | |
dc.contributor.author | Bronstein, Joel | |
dc.contributor.author | Nawer, Humaira | |
dc.contributor.author | Xu, Tao | |
dc.contributor.author | Figueroa, Maria | |
dc.contributor.author | Muntean, Andrew G. | |
dc.contributor.author | Hess, Jay L. | |
dc.contributor.department | Department of Medicine, IU School of Medicine | en_US |
dc.date.accessioned | 2016-02-26T20:18:26Z | |
dc.date.available | 2016-02-26T20:18:26Z | |
dc.date.issued | 2014-07-08 | |
dc.description.abstract | Homeobox A9 (HOXA9) is a homeodomain-containing transcription factor that plays a key role in hematopoietic stem cell expansion and is commonly deregulated in human acute leukemias. A variety of upstream genetic alterations in acute myeloid leukemia (AML) lead to overexpression of HOXA9, almost always in association with overexpression of its cofactor meis homeobox 1 (MEIS1) . A wide range of data suggests that HOXA9 and MEIS1 play a synergistic causative role in AML, although the molecular mechanisms leading to transformation by HOXA9 and MEIS1 remain elusive. In this study, we identify CCAAT/enhancer binding protein alpha (C/EBPα) as a critical collaborator required for Hoxa9/Meis1-mediated leukemogenesis. We show that C/EBPα is required for the proliferation of Hoxa9/Meis1-transformed cells in culture and that loss of C/EBPα greatly improves survival in both primary and secondary murine models of Hoxa9/Meis1-induced leukemia. Over 50% of Hoxa9 genome-wide binding sites are cobound by C/EBPα, which coregulates a number of downstream target genes involved in the regulation of cell proliferation and differentiation. Finally, we show that Hoxa9 represses the locus of the cyclin-dependent kinase inhibitors Cdkn2a/b in concert with C/EBPα to overcome a block in G1 cell cycle progression. Together, our results suggest a previously unidentified role for C/EBPα in maintaining the proliferation required for Hoxa9/Meis1-mediated leukemogenesis. | en_US |
dc.identifier.citation | Collins, C., Wang, J., Miao, H., Bronstein, J., Nawer, H., Xu, T., … Hess, J. L. (2014). C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis. Proceedings of the National Academy of Sciences of the United States of America, 111(27), 9899–9904. http://doi.org/10.1073/pnas.1402238111 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/8544 | |
dc.language.iso | en_US | en_US |
dc.publisher | PNAS | en_US |
dc.relation.isversionof | 10.1073/pnas.1402238111 | en_US |
dc.relation.journal | Proceedings of the National Academy of Sciences of the United States of America | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Enhancer | en_US |
dc.subject | Gene regulation | en_US |
dc.title | C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis | en_US |
dc.type | Article | en_US |