| Title |
ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia
|
|---|---|
| Published in |
Cancer Cell, March 2017
|
| DOI | 10.1016/j.ccell.2017.02.006 |
| Pubmed ID | |
| Authors |
Cécile Thirant, Cathy Ignacimouttou, Cécile K. Lopez, M’Boyba Diop, Lou Le Mouël, Clarisse Thiollier, Aurélie Siret, Phillipe Dessen, Zakia Aid, Julie Rivière, Philippe Rameau, Céline Lefebvre, Mehdi Khaled, Guy Leverger, Paola Ballerini, Arnaud Petit, Hana Raslova, Catherine L. Carmichael, Benjamin T. Kile, Eric Soler, John D. Crispino, Christian Wichmann, Françoise Pflumio, Jürg Schwaller, William Vainchenker, Camille Lobry, Nathalie Droin, Olivier A. Bernard, Sébastien Malinge, Thomas Mercher |
| 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. |
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X Demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 6 | 38% |
| France | 3 | 19% |
| Belgium | 1 | 6% |
| Italy | 1 | 6% |
| Austria | 1 | 6% |
| Unknown | 4 | 25% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 8 | 50% |
| Scientists | 6 | 38% |
| Science communicators (journalists, bloggers, editors) | 1 | 6% |
| Unknown | 1 | 6% |
Mendeley demographics
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Italy | 1 | 1% |
| Austria | 1 | 1% |
| Unknown | 97 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 19 | 19% |
| Researcher | 14 | 14% |
| Student > Bachelor | 10 | 10% |
| Student > Master | 7 | 7% |
| Student > Postgraduate | 5 | 5% |
| Other | 11 | 11% |
| Unknown | 33 | 33% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 25 | 25% |
| Agricultural and Biological Sciences | 19 | 19% |
| Medicine and Dentistry | 12 | 12% |
| Immunology and Microbiology | 2 | 2% |
| Arts and Humanities | 1 | 1% |
| Other | 6 | 6% |
| Unknown | 34 | 34% |