ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia

Cecile Thirant; Cathy Ignacimouttou; Cecile K. Lopez; M'Boyba Diop; Lou Le Mouel; Clarisse Thiollier; Aurelie Siret; Phillipe Dessen; Zakia Aid; Julie Riviere; Philippe Rameau; Ce ' Line Lefebvre; Mehdi Khaled; Guy Leverger; Paola Ballerini; Arnaud Petit; Hana Raslova; Catherine L. Carmichael; Benjamin T. Kile; Eric Soler; John D. Crispino; Christian Wichmann; Francoise Pflumio; Jurg Schwaller; William Vainchenker; Camille Lobry; Nathalie Droin; Olivier A. Bernard; Sebastien Malinge; Thomas Mercher

doi:10.1016/j.ccell.2017.02.006

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ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia

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ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia

Cecile Thirant, Cathy Ignacimouttou, Cecile K. Lopez, M'Boyba Diop, Lou Le Mouel, Clarisse Thiollier, Aurelie Siret, Phillipe Dessen, Zakia Aid, Julie Riviere, …

Cancer cell, Vol.31(3), pp.452-465

13/03/2017

DOI: https://doi.org/10.1016/j.ccell.2017.02.006

PMID: 28292442

Résumé

Cell Biology

Life Sciences & Biomedicine

Oncology

Science & Technology

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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Titre: ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia
Créateurs - sans rôle: Cecile Thirant - Inserm
Cathy Ignacimouttou - Inserm
Cecile K. Lopez - Inserm
M'Boyba Diop - Gustave Roussy, F-94800 Villejuif, France
Lou Le Mouel - Gustave Roussy, F-94800 Villejuif, France
Clarisse Thiollier - Gustave Roussy, F-94800 Villejuif, France
Aurelie Siret - Inserm
Phillipe Dessen - Inst Gustave Roussy, Equipe Labellisee Ligue Canc, INSERM, U1170, 39 Rue Camille Desmoulins, F-94800 Villejuif, France
Zakia Aid - Inserm
Julie Riviere - Inserm
Philippe Rameau - Gustave Roussy, F-94800 Villejuif, France
Ce ' Line Lefebvre - Gustave Roussy, F-94800 Villejuif, France
Mehdi Khaled - Gustave Roussy, F-94800 Villejuif, France
Guy Leverger - Hop Trousseau, AP HP, F-75012 Paris, France
Paola Ballerini - Assistance Publique – Hôpitaux de Paris
Arnaud Petit - Assistance Publique – Hôpitaux de Paris
Hana Raslova - Inst Gustave Roussy, Equipe Labellisee Ligue Canc, INSERM, U1170, 39 Rue Camille Desmoulins, F-94800 Villejuif, France
Catherine L. Carmichael - Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia
Benjamin T. Kile - Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia
Eric Soler - INSERM, UMR967, F-92265 Fontenay Aux Roses, France
John D. Crispino - Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA
Christian Wichmann - Ludwig Maximilian Univ Hosp, Dept Transfus Med Cell Therapeut & Hemostaseol, Munich, Germany
Francoise Pflumio - Inserm
Jurg Schwaller - Univ Basel, Univ Childrens Hosp Beider Basel UKBB, Dept Biomed, CH-4031 Basel, Switzerland
William Vainchenker - Inst Gustave Roussy, Equipe Labellisee Ligue Canc, INSERM, U1170, 39 Rue Camille Desmoulins, F-94800 Villejuif, France
Camille Lobry - Inserm
Nathalie Droin - Inst Gustave Roussy, Equipe Labellisee Ligue Canc, INSERM, U1170, 39 Rue Camille Desmoulins, F-94800 Villejuif, France
Olivier A. Bernard - Inserm
Sebastien Malinge - Inst Gustave Roussy, Equipe Labellisee Ligue Canc, INSERM, U1170, 39 Rue Camille Desmoulins, F-94800 Villejuif, France
Thomas Mercher - Inst Gustave Roussy, Equipe Labellisee Ligue Canc, INSERM, U1170, 39 Rue Camille Desmoulins, F-94800 Villejuif, France
Détails de publication: Cancer cell, Vol.31(3), pp.452-465
Éditeur: Elsevier
Nombre de pages: 14
Note de subvention: Fondation Gustave Roussy Federation Enfants et Sante and Societe Francaise de lutte contre les Cancers et les Leucemies de l'Enfant et l'Adolescent (SFCE: CAMELIAT project) Fondation ARC Canceropole Ile de France; Region Ile-de-France DJCLS-EHA-2009-F-09/02 / Jose Carreras EHA award; European Hematology Association PLBIO-2014-176 / Institut National Du Cancer; Institut National du Cancer (INCA) France R14120LL / Lady Tata Foundation FdF-00057925 / Fondation de France ALF-2015/13 / Association Laurette Fugain FRM-ING20150532273 / Fondation pour la Recherche Medicale
Identifiants: 99139651709311
Unité académique: Institut de Génétique Moléculaire de Montpellier - IGMM
Langue: English
Type de ressource: Journal article