hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | STUANI, Lucille | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | SABATIER, Marie | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | SALAND, Estelle | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | COGNET, Guillaume | |
hal.structure.identifier | Métabolisme et Xénobiotiques [ToxAlim-MeX] | |
dc.contributor.author | POUPIN, Nathalie | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | BOSC, Claudie | |
hal.structure.identifier | Médicaments et Technologies pour la Santé [MTS] | |
hal.structure.identifier | Service de Pharmacologie et Immunoanalyse [SPI] | |
hal.structure.identifier | Laboratoire Innovations en Spectrométrie de Masse pour la santé [LI-MS] | |
hal.structure.identifier | Small molecule analysis and omics [SMART-OMICS] | |
hal.structure.identifier | MetaboHUB-IDF | |
hal.structure.identifier | CEA- Saclay [CEA] | |
hal.structure.identifier | Université Paris-Saclay | |
dc.contributor.author | CASTELLI, Florence | |
hal.structure.identifier | Toulouse Biotechnology Institute [TBI] | |
dc.contributor.author | GALES, Lara | |
hal.structure.identifier | Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM] | |
dc.contributor.author | TURTOI, Evgenia | |
hal.structure.identifier | Centre de Recherche en Cancérologie de Marseille [CRCM] | |
dc.contributor.author | MONTERSINO, Camille | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | FARGE, Thomas | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | BOET, Emeline | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | BROIN, Nicolas | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | LARRUE, Clément | |
hal.structure.identifier | MD Anderson Cancer Center [Houston] | |
dc.contributor.author | BARAN, Natalia | |
hal.structure.identifier | Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM] | |
dc.contributor.author | CISSÉ, Madi | |
hal.structure.identifier | Institut National de la Santé et de la Recherche Médicale [INSERM] | |
dc.contributor.author | CONTI, Marc | |
hal.structure.identifier | Institut National de la Santé et de la Recherche Médicale [INSERM] | |
dc.contributor.author | LORIC, Sylvain | |
hal.structure.identifier | Luxembourg Institute of Health [LIH] | |
dc.contributor.author | KAOMA, Tony | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | HUCTEAU, Alexis | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | ZAVORITI, Aliki | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | SAHAL, Ambrine | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | MOUCHEL, Pierre-Luc | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | GOTANÈGRE, Mathilde | |
hal.structure.identifier | Biologie du fruit et pathologie [BFP] | |
dc.contributor.author | CASSAN, Cédric | |
hal.structure.identifier | ToxAlim [ToxAlim] | |
dc.contributor.author | FERNANDO, Laurent | |
hal.structure.identifier | MD Anderson Cancer Center [Houston] | |
dc.contributor.author | WANG, Feng | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | HOSSEINI, Mohsen | |
hal.structure.identifier | Laboratoire d'Etude du Métabolisme des Médicaments [LEMM] | |
dc.contributor.author | CHU-VAN, Emeline | |
hal.structure.identifier | Institut National de la Santé et de la Recherche Médicale [INSERM] | |
dc.contributor.author | LE CAM, Laurent | |
hal.structure.identifier | University of Pennsylvania | |
dc.contributor.author | CARROLL, Martin | |
hal.structure.identifier | University of Pennsylvania | |
dc.contributor.author | SELAK, Mary | |
hal.structure.identifier | Centre de Recherche en Cancérologie de Marseille [CRCM] | |
dc.contributor.author | VEY, Norbert | |
hal.structure.identifier | Centre de Recherche en Cancérologie de Marseille [CRCM] | |
dc.contributor.author | CASTELLANO, Rémy | |
hal.structure.identifier | Laboratoire d'Etude du Métabolisme des Médicaments [LEMM] | |
hal.structure.identifier | Laboratoire Innovations en Spectrométrie de Masse pour la santé [LI-MS] | |
hal.structure.identifier | Service de Pharmacologie et Immunoanalyse [SPI] | |
hal.structure.identifier | Médicaments et Technologies pour la Santé [MTS] | |
hal.structure.identifier | MetaboHUB-IDF | |
dc.contributor.author | FENAILLE, François | |
hal.structure.identifier | Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM] | |
dc.contributor.author | TURTOI, Andrei | |
hal.structure.identifier | Université de Montpellier [UM] | |
dc.contributor.author | CAZALS, Guillaume | |
hal.structure.identifier | Réseau régional de cancérologie Onco-Occitanie | |
dc.contributor.author | BORIES, Pierre | |
hal.structure.identifier | Biologie du fruit et pathologie [BFP] | |
dc.contributor.author | GIBON, Yves | |
hal.structure.identifier | Agios Pharmaceuticals | |
dc.contributor.author | NICOLAY, Brandon | |
hal.structure.identifier | Agios Pharmaceuticals | |
dc.contributor.author | RONSEAUX, Sébastien | |
hal.structure.identifier | MD Anderson Cancer Center [Houston] | |
dc.contributor.author | MARSZALEK, Joseph | |
hal.structure.identifier | MD Anderson Cancer Center [Houston] | |
dc.contributor.author | TAKAHASHI, Koichi | |
hal.structure.identifier | MD Anderson Cancer Center [Houston] | |
dc.contributor.author | DINARDO, Courtney | |
hal.structure.identifier | MD Anderson Cancer Center [Houston] | |
dc.contributor.author | KONOPLEVA, Marina | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | PANCALDI, Véra | |
hal.structure.identifier | Centre de Recherche en Cancérologie de Marseille [CRCM] | |
dc.contributor.author | COLLETTE, Yves | |
hal.structure.identifier | Toulouse Biotechnology Institute [TBI] | |
dc.contributor.author | BELLVERT, Floriant | |
hal.structure.identifier | Métabolisme et Xénobiotiques [ToxAlim-MeX] | |
dc.contributor.author | JOURDAN, Fabien | |
hal.structure.identifier | Institut de Recherche en Cancérologie de Montpellier [IRCM - U1194 Inserm - UM] | |
dc.contributor.author | LINARES, Laetitia | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
dc.contributor.author | RÉCHER, Christian | |
hal.structure.identifier | Toulouse Biotechnology Institute [TBI] | |
dc.contributor.author | PORTAIS, Jean-Charles | |
hal.structure.identifier | Centre de Recherches en Cancérologie de Toulouse [CRCT] | |
hal.structure.identifier | Centre Hospitalier Universitaire de Toulouse [CHU Toulouse] | |
dc.contributor.author | SARRY, Jean-Emmanuel | |
dc.date.issued | 2021-03-24 | |
dc.identifier.issn | 0022-1007 | |
dc.description.abstractEn | Mutations in IDH induce epigenetic and transcriptional reprogramming, differentiation bias, and susceptibility to mitochondrial inhibitors in cancer cells. Here, we first show that cell lines, PDXs, and patients with acute myeloid leukemia (AML) harboring an IDH mutation displayed an enhanced mitochondrial oxidative metabolism. Along with an increase in TCA cycle intermediates, this AML-specific metabolic behavior mechanistically occurred through the increase in electron transport chain complex I activity, mitochondrial respiration, and methylation-driven CEBPα-induced fatty acid β-oxidation of IDH1 mutant cells. While IDH1 mutant inhibitor reduced 2-HG oncometabolite and CEBPα methylation, it failed to reverse FAO and OxPHOS. These mitochondrial activities were maintained through the inhibition of Akt and enhanced activation of peroxisome proliferator-activated receptor-γ coactivator-1 PGC1α upon IDH1 mutant inhibitor. Accordingly, OxPHOS inhibitors improved anti-AML efficacy of IDH mutant inhibitors in vivo. This work provides a scientific rationale for combinatory mitochondrialtargeted therapies to treat IDH mutant AML patients, especially those unresponsive to or relapsing from IDH mutant inhibitors. | |
dc.description.sponsorship | Cancer et Pharmacologie : Projet de Toulouse-Oncopole et de sa Région | |
dc.description.sponsorship | Analyse intégrée de la résistance dans les cancers hématologiques | |
dc.description.sponsorship | Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation | |
dc.language.iso | en | |
dc.publisher | Rockefeller University Press | |
dc.rights.uri | http://creativecommons.org/licenses/by/ | |
dc.title.en | Mitochondrial metabolism supports resistance to IDH mutant inhibitors in acute myeloid leukemia | |
dc.type | Article de revue | |
dc.identifier.doi | 10.1084/jem.20200924 | |
dc.subject.hal | Sciences du Vivant [q-bio] | |
bordeaux.journal | Journal of Experimental Medicine | |
bordeaux.page | e20200924 | |
bordeaux.volume | 218 | |
bordeaux.issue | 5 | |
bordeaux.peerReviewed | oui | |
hal.identifier | hal-03563454 | |
hal.version | 1 | |
hal.popular | non | |
hal.audience | Internationale | |
hal.origin.link | https://hal.archives-ouvertes.fr//hal-03563454v1 | |
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