ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia
- Author(s)
- Thirant, C; Ignacimouttou, C; Lopez, CK; Diop, M; Le Mouel, L; Thiollier, C; Siret, A; Dessen, P; Aid, Z; Riviere, J; Rameau, P; Lefebvre, C; Khaled, M; Leverger, G; Ballerini, P; Petit, A; Raslova, H; Carmichael, CL; Kile, BT; Soler, E; Crispino, JD; Wichmann, C; Pflumio, F; Schwaller, J; Vainchenker, W; Lobry, C; Droin, N; Bernard, OA; Malinge, S; Mercher, T;
- Details
- Publication Year 2017-03-13,Volume 31,Issue #3,Page 452-465
- Journal Title
- Cancer Cell
- Publication Type
- Journal Article
- Abstract
- Chimeric transcription factors are a hallmark of human leukemia, but the molecular mechanisms by which they block differentiation and promote aberrant self-renewal remain unclear. Here, we demonstrate that the ETO2-GLIS2 fusion oncoprotein, which is found in aggressive acute megakaryoblastic leukemia, confers megakaryocytic identity via the GLIS2 moiety while both ETO2 and GLIS2 domains are required to drive increased self-renewal properties. ETO2-GLIS2 directly binds DNA to control transcription of associated genes by upregulation of expression and interaction with the ETS-related ERG protein at enhancer elements. Importantly, specific interference with ETO2-GLIS2 oligomerization reverses the transcriptional activation at enhancers and promotes megakaryocytic differentiation, providing a relevant interface to target in this poor-prognosis pediatric leukemia.
- Publisher
- Cell Press
- Research Division(s)
- Chemical Biology
- PubMed ID
- 28292442
- Publisher's Version
- https://doi.org/10.1016/j.ccell.2017.02.006
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-04-12 10:42:25
Last Modified: 2017-04-12 11:47:19