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2. Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia

Author

Jourdan, Eric, Boissel, Nicolas, Chevret, Sylvie, Delabesse, Eric, Renneville, Aline, Cornillet, Pascale, Blanchet, Odile, Cayuela, Jean-Michel, Recher, Christian, Raffoux, Emmanuel, Delaunay, Jacques, Pigneux, Arnaud, Bulabois, Claude-Eric, Berthon, Céline, Pautas, Cécile, Vey, Norbert, Lioure, Bruno, Thomas, Xavier, Luquet, Isabelle, Terré, Christine, Guardiola, Philippe, Béné, Marie C., Preudhomme, Claude, Ifrah, Norbert, and Dombret, Hervé

Published
2013
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3. Daunorubicin and Its Active Metabolite Pharmacokinetic Profiles in Acute Myeloid Leukaemia Patients: A Pharmacokinetic Ancillary Study of the BIG-1 Trial

Author

Drevin, Guillaume, primary, Briet, Marie, additional, Bazzoli, Caroline, additional, Gyan, Emmanuel, additional, Schmidt, Aline, additional, Dombret, Hervé, additional, Orvain, Corentin, additional, Giltat, Aurelien, additional, Recher, Christian, additional, Ifrah, Norbert, additional, Guardiola, Philippe, additional, Hunault-Berger, Mathilde, additional, and Abbara, Chadi, additional

Published
2022
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4. Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities

Author

Perrot, Aurore, Luquet, Isabelle, Pigneux, Arnaud, Mugneret, Francine, Delaunay, Jacques, Harousseau, Jean-Luc, Barin, Carole, Cahn, Jean-Yves, Guardiola, Philippe, Himberlin, Chantal, Recher, Christian, Vey, Norbert, Lioure, Bruno, Ojeda-Uribe, Mario, Fegueux, Nathalie, Berthou, Christian, Randriamalala, Edouard, Béné, Marie C., Ifrah, Norbert, and Witz, Francis

Published
2011
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5. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs)

Author

Kosmider, Olivier, Gelsi-Boyer, Véronique, Cheok, Meyling, Grabar, Sophie, Della-Valle, Véronique, Picard, Françoise, Viguié, Franck, Quesnel, Bruno, Beyne-Rauzy, Odile, Solary, Eric, Vey, Norbert, Hunault-Berger, Mathilde, Fenaux, Pierre, Mansat-De Mas, Véronique, Delabesse, Eric, Guardiola, Philippe, Lacombe, Catherine, Vainchenker, William, Preudhomme, Claude, Dreyfus, François, Bernard, Olivier A., Birnbaum, Daniel, and Fontenay, Michaëla

Published
2009
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6. Bromodomain‐dependent stage‐specific male genome programming by Brdt

Author

Gaucher, Jonathan, Boussouar, Fayçal, Montellier, Emilie, Curtet, Sandrine, Buchou, Thierry, Bertrand, Sarah, Hery, Patrick, Jounier, Sylvie, Depaux, Arnaud, Vitte, Anne‐Laure, Guardiola, Philippe, Pernet, Karin, Debernardi, Alexandra, Lopez, Fabrice, Holota, Hélène, Imbert, Jean, Wolgemuth, Debra J, Gérard, Matthieu, Rousseaux, Sophie, and Khochbin, Saadi

Published
2012
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7. Transcriptomic features of tumour- infiltrating CD4 low CD8 high double positive αβ T cells in melanoma

Author

Parrot, Tiphaine, Oger, Romain, Allard, Mathilde, Desfrançois, Juliette, Raingeard de la Blétìère, Diane, Coutolleau, Anne, Preisser, Laurence, Khammari, Amir, Dréno, Brigitte, Delneste, Yves, Guardiola, Philippe, Fradin, Delphine, Gervois, Nadine, Anti-Tumor Immunosurveillance and Immunotherapy (CRCINA-ÉQUIPE 3), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), LabEX IGO Immunothérapie Grand Ouest, Nuclear Oncology (CRCINA-ÉQUIPE 13), Plateforme CYTOCELL Nantes (CRCINA-CYTOCELL), Service de Génomique Onco-Hématologique [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Cancéropôle Grand OuestRégion Pays de la LoireLigue Nationale contre le Cancer, ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), Bernardo, Elizabeth, and Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID

Subjects
[SDV.CAN] Life Sciences [q-bio]/Cancer, lcsh:R, lcsh:Medicine, lcsh:Q, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:Science
Abstract

International audience; Peripheral CD4 + CD8 + double positive (DP) T cells are a phenotypically and functionally heterogeneous population depending on their origin and pathologic context. We previously identified among tumour infiltrating lymphocytes in melanoma, a tumour-reactive MHC class-I restricted CD4 low CD8 high DP αβ T-cell subpopulation with CD4-like function. In this study, we used an in-depth comparative transriptomic analysis of intra-melanoma DP T cells and CD4 and CD8 single positive (SP) T cells, to better comprehend the origin of this DP phenotype, and define the transcriptomic signature of activated DP T cells. We observed that intra-melanoma DP T cells were transcriptome-wise closer to their CD8 SP T-cell counterparts in terms of number of genes differentially expressed (97 in common with CD8 SP T cells and 15 with CD4 SP T cells) but presented hallmarks of a transition to a CD4-like functional profile (CD40LG) with a decreased cytotoxic signature (KLRC1) in favour of an increased cytokine-receptor interaction signature (IL4, IL24, IL17A…). This unleashed CD4-like program could be the results of the observed unbalanced expression of the THPOK/Runx3 transcription factors in DP T cells. Overall, this study allow us to speculate that intra-melanoma DP T cells arise from CD8 SP T cells being reprogrammed to a helper function. Contrary to the CD4 + CD8 + double positive (DP) thymocytes, well described as a T cell development stage, peripheral DP αβ T cells had attracted less attention mostly because of their weak frequency in the peripheral blood of healthy human donors (1 to 3%) 1,2. Nonetheless, following diverse inflammatory processes from viral or parasitic infections 3-5 , to autoimmune diseases 6,7 or cancer 8-14 , this subpopulation can become quite predominant in the blood or in the inflamed tissue/organ. This suggests a causal relationship between DP T cell emergence and disease. From these studies, DP T cells appeared as a more heterogeneous population than initially thought. Based on the co-expression level of the CD8 and CD4 co-receptors, peripheral DP T cells can be subdivided into three major subtypes: (i) the CD4 high CD8 low phenotype expressing the CD8αα homodimer, (ii) the CD4 high CD8 high phenotype and (iii) the CD4 low CD8 high phenotype both expressing the CD8αβ heterodimer 15,16. Although not always clearly demonstrated, these diverse phenotypes are presumably resulting from diverse origins. Thus, it has been proposed that CD4 high CD8 low DP T cells derive from peripheral CD4 T cells that following activation with the appropriate co-stimuli such as IL-4, TGF-β or retinoic acid can induce the CD8αα co-receptor expression at a low level 17. On the other hand, the CD4 low CD8 high phenotype is considered to be emerging from peripheral CD8 T cells that after activation with strong stimuli can reexpress the CD4 co-receptor at a low level 18,19. Regarding the CD4 high CD8 high phenotype, less is known and either a thymus or a peripheral origin can be considered. In our previous work, we have described the enrichment in the tumour infiltrate of several solid cancers including melanoma, of a class-I-restricted DP T-cell population presenting the CD4 low CD8 high phenotype 9,10. This population was not increased in the peripheral blood suggesting the influence of the tumour microenviron-ment upon the development of DP T cells. Because of their class-I restriction and their CD4 low CD8 high phenotype

Published
2020
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9. Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

Author

Vignon, Christine, primary, Debeissat, Christelle, additional, Bourgeais, Jérôme, additional, Gallay, Nathalie, additional, Kouzi, Farah, additional, Anginot, Adrienne, additional, Picou, Frédéric, additional, Guardiola, Philippe, additional, Ducrocq, Elfi, additional, Foucault, Amélie, additional, Ravalet, Noémie, additional, Le Nail, Louis-Romée, additional, Domenech, Jorge, additional, Béné, Marie-Christine, additional, Le Bousse-Kerdilès, Marie-Caroline, additional, Gyan, Emmanuel, additional, and Herault, Olivier, additional

Published
2020
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10. Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction

Author

Chabrun, Floris, primary, Huetz, Noémie, additional, Dieu, Xavier, additional, Rousseau, Guillaume, additional, Bouzillé, Guillaume, additional, Chao de la Barca, Juan Manuel, additional, Procaccio, Vincent, additional, Lenaers, Guy, additional, Blanchet, Odile, additional, Legendre, Guillaume, additional, Mirebeau-Prunier, Delphine, additional, Cuggia, Marc, additional, Guardiola, Philippe, additional, Reynier, Pascal, additional, and Gascoin, Geraldine, additional

Published
2020
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12. Haematopoietic stem cell transplantation for vasculitis including Behçet’s disease and polychondritis: a retrospective analysis of patients recorded in the European Bone Marrow Transplantation and European League Against Rheumatism databases and a review of the literature

Author

Daikeler, Thomas, Kötter, Ina, Tyndall, Chiara Bocelli, Apperley, Jane, Attarbaschi, Andishe, Guardiola, Philippe, Gratwohl, Alois, Jantunen, Esa, Marmont, Alberto, Porretto, Ferdinando, Musso, Maurizio, Maurer, Britta, Rinaldi, Nadia, Saccardi, Riccardo, and Tyndall, Alan

Published
2007

16. Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples

Author

de la Blétière Diane Raingeard, Blanchet Odile, Cornillet-Lefèbvre Pascale, Coutolleau Anne, Baranger Laurence, Geneviève Franck, Luquet Isabelle, Hunault-Berger Mathilde, Beucher Annaelle, Schmidt-Tanguy Aline, Zandecki Marc, Delneste Yves, Ifrah Norbert, and Guardiola Philippe

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n = 101) and/or poor quality control criteria (n = 10) (test set). Results With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.

Published
2012
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17. Cost of cancer diagnosis using next-generation sequencing targeted gene panels in routine practice: a nationwide French study (vol 26, pg 314, 2018)

Author

Touzani, Rajae, Kossi, Dede Sika, Zhaomin, Zou, Charrier, Nathanael, Baffert, Sandrine, Barillot, Emmanuel, Bezieau, Stephane, Borget, Isabelle, Coppin, Lucie, Descapentries, Clothilde, Durand-Zaleski, Isabelle, Forget, Sebastien, Frebourd, Thierry, Guardiola, Philippe, Goardon, Nicolas, Houdayer, Claude, Hupe, Philippe, Lacroix, Ludovic, Leclerc, Julie, Lespagnol, Alexandra, Longuemare, Stephanie, Marino, Patricia, Mosser, Jean, Odou, Marie-Francoise, Perrier, Lionel, Preudhomme, Claude, Revillion, Francoise, Rouleau, Etienne, Sevenet, Nicolas, Soubeyran, Isabelle, Vaur, Dominique, Grp, NGSEco, DUFOUR, Jean-Charles, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Published
2018
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18. Retrospective comparison of bone marrow and granulocyte colony-stimulating factor–mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes

Author

Guardiola, Philippe, Runde, Volker, Bacigalupo, Andrea, Ruutu, Tapani, Locatelli, Franco, Boogaerts, Marc A., Pagliuca, Antonio, Cornelissen, Jan J., Schouten, Harry C., Carreras, Enric, Finke, Jürgen, van Biezen, Anja, Brand, Ronald, Niederwieser, Dietger, Gluckman, Eliane, and de Witte, Theo M.

Published
2002
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20. Association of complementation group and mutation type with clinical outcome in Fanconi anemia

Author

Faivre, Laurence, Guardiola, Philippe, Lewis, Cathryn, Dokal, Inderjeet, Ebell, Wolfram, Zatterale, Ariana, Altay, Cigdem, Poole, Janet, Stones, David, Kwee, Mei Lan, van Weel-Sipman, Margreet, Havenga, Charmaine, Morgan, Neil, de Winter, Johan, Digweed, Martin, Savoia, Anna, Pronk, Jan, de Ravel, Thomas, Jansen, Stander, Joenje, Hans, Gluckman, Eliane, and Mathew, Christopher G.

Published
2000
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24. Allogeneic Stem Cell Transplantation for Agnogenic Myeloid Metaplasia: A European Group for Blood and Marrow Transplantation, Société Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study

Author

Guardiola, Philippe, Anderson, Jeanne E., Bandini, Giuseppe, Cervantes, Francisco, Runde, Volker, Arcese, William, Bacigalupo, Andrea, Przepiorka, Donna, O'Donnell, Margaret R., Polchi, Paola, Buzyn, Agnès, Sutton, Laurent, Cazals-Hatem, Dominique, Sale, George, de Witte, Theo, Deeg, H. Joachim, and Gluckman, Eliane

Published
1999
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25. Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells

Author

Morozumi, Yuichi, Boussouar, Fayçal, Tan, Minjia, Chaikuad, Apirat, Jamshidikia, Mahya, Colak, Gozde, He, Huang, Nie, Litong, Petosa, Carlo, De Dieuleveult, Maud, Curtet, Sandrine, Vitte, Anne-Laure, Rabatel, Clothilde, Debernardi, Alexandra, François-Loïc, Cosset, Verhoeyen, Els, Emadali, Anouk, Schweifer, Norbert, Gianni, Davide, Gut, Marta, Guardiola, Philippe, Rousseaux, Sophie, Gérard, Matthieu, Knapp, Stefan, Zhao, Yingming, Khochbin, Saadi, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), The Chemical Proteomics Center and State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Structural Genomics Consortium, University of Oxford, Nuffield Department of Clinical Medicine [Oxford], Ben May Department of Cancer Research, The University of Chicago Medicine, Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe 'Contrôle Métabolique des Morts Cellulaires' (INSERM U1065 - C3M), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Boehringer Ingelheim RCV, Centre for Genomic Regulation [Barcelona] (CRG), Universitat Pompeu Fabra [Barcelona] (UPF)-Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of Oxford [Oxford], Target Discovery Institute (TDI), Nuffield Department of Clinical Medicine, Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Centre International de Recherche en Infectiologie ( CIRI ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-École normale supérieure - Lyon ( ENS Lyon ), Centre for Genomic Regulation [Barcelona] ( CRG ), Universitat Pompeu Fabra [Barcelona]-Centro Nacional de Analisis Genomico [Barcelona] ( CNAG ), Inserm u892, Centre de Recherches en Cancérologie, Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adenosine Triphosphatases, Male, Proteomics, histone turnover, Chromatin Immunoprecipitation, germ cells, Genome, Pax3, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], FACT, epidrug, Acetylation, Cell Differentiation, Article, Chromatin, Nucleosomes, DNA-Binding Proteins, histone chaperone, ATPases Associated with Diverse Cellular Activities, Humans, cancer drug target, Embryonic Stem Cells, Cell Proliferation, Protein Binding
Abstract

International audience; Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics, and RNA-seq experiments in embryonic stem cells where Atad2 is normally highly expressed, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication, and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells Atad2 becomes critical in sustaining specific gene expression programmes, controlling proliferation and differentiation. Altogether, this work defines Atad2 as a facilitator of general chromatin-templated activities such as transcription.

Published
2016
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28. CD40L confers helper functions to human intra-melanoma class-I-restricted CD4+CD8+double positive T cells

Author

Parrot, Tiphaine, primary, Oger, Romain, additional, Benlalam, Houssem, additional, Raingeard de la Blétière, Diane, additional, Jouand, Nicolas, additional, Coutolleau, Anne, additional, Preisser, Laurence, additional, Khammari, Amir, additional, Dréno, Brigitte, additional, Guardiola, Philippe, additional, Delneste, Yves, additional, Labarrière, Nathalie, additional, and Gervois, Nadine, additional

Published
2016
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29. GATA2 Expression Level in Chronic Myeloid Leukemia (CML) Patients Correlates with Their Prognostic Scores and Is Associated with Disease Stage at Diagnosis

Author

Guardiola, Philippe, primary, Orvain, Corentin, additional, Cross, Nick C.P., additional, Gardembas, Martine, additional, Spentchian, Marc, additional, Pedrono, Estelle, additional, Lambert, Diane, additional, Coutolleau, Anne, additional, Bouvier, Anne, additional, Blanchet, Odile, additional, Piard, Nicole, additional, Ifrah, Norbert, additional, Giles, Frank, additional, Hochhaus, Andreas, additional, Radich, Jerald P., additional, and Rousselot, Philippe, additional

Published
2015
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30. HFE Gene Mutation Status Predicts Response to Gemtuzumab Ozogamicin in AML

Author

Paubelle, Etienne, primary, Marceau, Alice, additional, Zylbersztejn, Florence, additional, Dussiot, Mickael, additional, Moura, Ivan Cruz, additional, Cornillet-Lefebvre, Pascale, additional, Delaunay, Jacques, additional, Burnett, Alan K., additional, Castaigne, Sylvie, additional, Guardiola, Philippe, additional, Ifrah, Norbert, additional, Dombret, Hervé, additional, Preudhomme, Claude, additional, Hills, Robert K, additional, and Hermine, Olivier, additional

Published
2015
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31. Safety and Long-Term Efficacy of Maintenance Therapy with Alternating Azacytidine (AZA) and Lenalidomide (Len) Cycles in Elderly (≥ 60) Fit Patients (Pts) with Poor Prognosis AML in First Complete Remission (CR) After LIA Induction. A Phase II Multicentric GOELAMS Trial

Author

Hunault, Mathilde, primary, Maillard, Nathalie, additional, Tanguy-Schmidt, Aline, additional, Himberlin, Chantal, additional, Choufi, Bachra, additional, Bonmati, Caroline, additional, Couturier, Marie Anne, additional, Deconinck, Eric, additional, Marolleau, Jean Pierre, additional, Orsini-Piocelle, Frédérique, additional, Delaunay, Jacques, additional, Tavernier, Emmanuelle, additional, Récher, Christian, additional, Lissandre, Severine, additional, Ojeda-Uribe, Mario, additional, Sanhes, Laurence, additional, Sutton, Laurent, additional, Banos, Anne, additional, Lioure, Bruno, additional, Bernard, Marc, additional, Bouscary, Didier, additional, Saad, Alain, additional, Rouille, Valérie, additional, Guardiola, Philippe, additional, Luquet, Isabelle, additional, Bene, Marie C, additional, Dreyfus, Francois, additional, Cahn, Jean-Yves, additional, Pigneux, Arnaud, additional, and Ifrah, Norbert, additional

Published
2015
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32. Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells

Author

Morozumi, Yuichi, primary, Boussouar, Fayçal, additional, Tan, Minjia, additional, Chaikuad, Apirat, additional, Jamshidikia, Mahya, additional, Colak, Gozde, additional, He, Huang, additional, Nie, Litong, additional, Petosa, Carlo, additional, de Dieuleveult, Maud, additional, Curtet, Sandrine, additional, Vitte, Anne-Laure, additional, Rabatel, Clothilde, additional, Debernardi, Alexandra, additional, Cosset, François-Loïc, additional, Verhoeyen, Els, additional, Emadali, Anouk, additional, Schweifer, Norbert, additional, Gianni, Davide, additional, Gut, Marta, additional, Guardiola, Philippe, additional, Rousseaux, Sophie, additional, Gérard, Matthieu, additional, Knapp, Stefan, additional, Zhao, Yingming, additional, and Khochbin, Saadi, additional

Published
2015
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35. Impact of High Body Surface Area on AML Outcome in Younger Patients: A Goelams Study

Author

Cahu, Xavier, primary, Carre, Martin, additional, Recher, Christian, additional, Gyan, Emmanuel, additional, Hamel, Jean-Francois, additional, Pigneux, Arnaud, additional, Vey, Norbert, additional, Guardiola, Philippe, additional, Delaunay, Jacques, additional, Jourdan, Eric, additional, Lioure, Bruno, additional, Bene, Marie-Christine, additional, Ifrah, Norbert, additional, and Cahn, Jean-Yves, additional

Published
2014
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37. Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks

Author

Deneberg, Stefan, Guardiola, Philippe, Lennartsson, Andreas, Qu, Ying, Gaidzik, Verena, Blanchet, Odile, Karimi, Mohsen, Bengtzén, Sofia, Nahi, Hareth, Uggla, Bertil, Tidefelt, Ulf, Höglund, Martin, Paul, Christer, Ekwall, Karl, Döhner, Konstanze, Lehmann, Sören, Deneberg, Stefan, Guardiola, Philippe, Lennartsson, Andreas, Qu, Ying, Gaidzik, Verena, Blanchet, Odile, Karimi, Mohsen, Bengtzén, Sofia, Nahi, Hareth, Uggla, Bertil, Tidefelt, Ulf, Höglund, Martin, Paul, Christer, Ekwall, Karl, Döhner, Konstanze, and Lehmann, Sören

Abstract

Cytogenetically normal acute myeloid leukemia (CN-AML) compose between 40% and 50% of all adult acute myeloid leukemia (AML) cases. In this clinically diverse group, molecular aberrations, such as FLT3-ITD, NPM1, and CEBPA mutations, recently have added to the prognostic accuracy. Aberrant DNA methylation is a hallmark of cancer, including AML. We investigated in total 118 CN-AML samples in a test and a validation cohort for genome-wide promoter DNA methylation with Illumina Methylation Bead arrays and compared them with normal myeloid precursors and global gene expression. IDH and NPM1 mutations were associated with different methylation patterns (P = .0004 and .04, respectively). Genome-wide methylation levels were elevated in IDH-mutated samples (P = .006). We observed a negative impact of DNA methylation on transcription. Genes targeted by Polycomb group (PcG) proteins and genes associated with bivalent histone marks in stem cells showed increased aberrant methylation in AML (P < .0001). Furthermore, high methylation levels of PcG target genes were independently associated with better progression-free survival (odds ratio = 0.47, P = .01) and overall survival (odds ratio = 0.36, P = .001). In summary, genome-wide methylation patterns show preferential methylation of PcG targets with prognostic impact in CN-AML.

Published
2011
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38. Maintenance Therapy With Alternating Azacytidine and Lenalidomide Cycles In Elderly (≥ 60) Fit Patients (Pts) With Poor Prognosis AML In First Complete Remission (CR) After Lia Induction. A Phase II Multicentric Goelams Trial

Author

Hunault-Berger, Mathilde, primary, Randriamalala, Edouard, additional, Schmidt-Tanguy, Aline, additional, Himberlin, Chantal, additional, Choufi, Bachra, additional, Bonmati, Caroline, additional, Cahn, Jean Yves, additional, marie-Anne Couturier, MD, additional, Deconinck, Eric, additional, Marolleau, Jean Pierre, additional, orisni-Piocelle, Frederique, additional, Delaunay, Jacques, additional, Tavernier, Emmanuelle, additional, Recher, Christian, additional, Lissandre, Severine, additional, Ojeda-Uribe, Mario, additional, Sanhes, Laurence, additional, Sutton, Laurent, additional, Banos, Anne, additional, Lioure, Bruno, additional, Lamy, Thierry, additional, Bouscary, Didier, additional, Saad, Alain, additional, Rouille, Valérie, additional, Guardiola, Philippe, additional, Luquet, Isabelle, additional, marie-Christine Bene, MD, additional, Dreyfus, Francois, additional, Ifrah, Norbert, additional, and Pigneux, Arnaud, additional

Published
2013
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39. Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

Author

Montellier, Emilie, primary, Boussouar, Fayçal, additional, Rousseaux, Sophie, additional, Zhang, Kai, additional, Buchou, Thierry, additional, Fenaille, François, additional, Shiota, Hitoshi, additional, Debernardi, Alexandra, additional, Héry, Patrick, additional, Curtet, Sandrine, additional, Jamshidikia, Mahya, additional, Barral, Sophie, additional, Holota, Hélène, additional, Bergon, Aurélie, additional, Lopez, Fabrice, additional, Guardiola, Philippe, additional, Pernet, Karin, additional, Imbert, Jean, additional, Petosa, Carlo, additional, Tan, Minjia, additional, Zhao, Yingming, additional, Gérard, Matthieu, additional, and Khochbin, Saadi, additional

Published
2013
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41. Large Artery Stiffening and Remodeling Are Independently Associated With All-Cause Mortality and Cardiovascular Events in Chronic Kidney Disease

Author

Karras, Alexandre, primary, Haymann, Jean-Philippe, additional, Bozec, Erwan, additional, Metzger, Marie, additional, Jacquot, Christian, additional, Maruani, Gerard, additional, Houillier, Pascal, additional, Froissart, Marc, additional, Stengel, Bénédicte, additional, Guardiola, Philippe, additional, Laurent, Stéphane, additional, Boutouyrie, Pierre, additional, and Briet, Marie, additional

Published
2012
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42. Outcome and Prognostic Factors in Patients with Mantle Cell Lymphoma Relapsing After Autologous Stem Cell Transplantation: A Retrospective Study of the EBMT

Author

Dietrich, Sascha, primary, Finel, Herve, additional, Boumendil, Ariane, additional, Avivi, Irit, additional, Volin, Liisa, additional, Cornelissen, Jan, additional, Walewski, Jan, additional, Schmid, Christoph, additional, de Witte, Theo M., additional, Schouten, Harry C., additional, Kaufmann, Martin, additional, Sebban, Catherine, additional, Trneny, Marek, additional, Kobbe, Guido, additional, Guardiola, Philippe, additional, Schetelig, Johannes, additional, Pfreundschuh, Michael, additional, Diez-Martin, Jose L., additional, Bordessoule, Dominique, additional, Robinson, Stephen, additional, and Dreger, Peter, additional

Published
2012
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43. Gene Mutations and Minimal Residual Disease (MRD) As Predictors of Remission Duration in Adults with Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) Treated with High-Dose Cytarabine (HDAC) - First Results of the Prospective French Intergroup CBF-2006 Trial

Author

Jourdan, Eric, primary, Boissel, Nicolas, additional, Blanchet, Odile, additional, Renneville, Aline, additional, Recher, Christian, additional, Raffoux, Emmanuel, additional, Cornillet-Lefebvre, Pascale, additional, Cayuela, Jean-Michel, additional, Delaunay, Jacques, additional, Pigneux, Arnaud, additional, Delabesse, Eric, additional, Bulabois, Claude-Eric, additional, Berthon, Céline, additional, Pautas, Cécile, additional, Vey, Norbert, additional, Lioure, Bruno, additional, Thomas, Xavier, additional, Contentin, Nathalie, additional, Randriamalala, Edouard, additional, Fegueux, Nathalie, additional, Béné, Marie-Christine, additional, Lejeune, Julie, additional, Guardiola, Philippe, additional, Preudhomme, Claude, additional, Ifrah, Norbert, additional, and Dombret, Hervé, additional

Published
2011
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44. Prognostic DNA methylation patterns in cytogenetically normal acute myeloid leukemia are predefined by stem cell chromatin marks

Author

Deneberg, Stefan, primary, Guardiola, Philippe, additional, Lennartsson, Andreas, additional, Qu, Ying, additional, Gaidzik, Verena, additional, Blanchet, Odile, additional, Karimi, Mohsen, additional, Bengtzén, Sofia, additional, Nahi, Hareth, additional, Uggla, Bertil, additional, Tidefelt, Ulf, additional, Höglund, Martin, additional, Paul, Christer, additional, Ekwall, Karl, additional, Döhner, Konstanze, additional, and Lehmann, Sören, additional

Published
2011
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45. Are Microarray-Derived Gene Expression Signatures Useful as a Routine Assay for Prognostic Evaluation of Acute Myeloid Leukemia Samples with Low Leukemic Blast Content ?.

Author

Guardiola, Philippe, primary, Lambert, Diane, additional, Cornillet-Lefebvre, Pascale, additional, Coutolleau, Anne, additional, Baranger, Laurence, additional, Genevieve, Franck, additional, Luquet, Isabelle, additional, Beucher, Annaelle, additional, Zandecki, Marc, additional, Ifrah, Norbert, additional, and Blanchet, Odile, additional

Published
2010
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47. Prognostic Value of the ‘Monosomal Karyotype’ Entity in Elderly Patients with AML: a GOELAMS Study of 186 Patients with Unfavourable Cytogenetic Abnormalities.

Author

Perrot, Aurore, primary, Luquet, Isabelle, additional, Pigneux, Arnaud, additional, Mugneret, Francine, additional, Delaunay, Jacques, additional, Harousseau, Jean-Luc, additional, Witz, Francis, additional, Barin, Carole, additional, Cahn, Jean-Yves, additional, Guardiola, Philippe, additional, Himberlin, Chantal, additional, Recher, Christian, additional, Vey, Norbert, additional, Lioure, Bruno, additional, Tournilhac, Olivier, additional, Fegueux, Nathalie, additional, Berthou, Christian, additional, Escoffre-Barbe, Martine, additional, Béné, Marie-Christine, additional, and Ifrah, Norbert, additional

Published
2009
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48. Improved Outcome with Androgens as Maintenance Treatment in Elderly Patients with Acute Myeloid Leukemia after ICL Regimen as Induction Therapy: Results of the GOELAMS SA-2002 Multicenter Phase III Randomized Open Trial

Author

Pigneux, Arnaud, primary, Himberlin, Chantal, primary, Hunault-Berger, Mathilde, primary, Witz, Francis, primary, Recher, Christian, primary, Harousseau, Jean-Luc, primary, Tournilhac, Olivier, primary, Berthou, Christian, primary, Escoffre-Barbe, Martine, primary, Guyotat, Denis, primary, Fegueux, Nathalie, primary, Delain, Martine, primary, Lioure, Bruno, primary, Jourdan, Eric, primary, Bouscary, Didier, primary, Legros, Laurence, primary, Milpied, Noel, primary, Bauduer, Frederic, primary, Perry, Frederic, primary, Luquet, Isabelle, primary, Bene, Marie-Christine, primary, Ifrah, Norbert, primary, Sotto, Jean-Jacques, primary, and Guardiola, Philippe, primary

Published
2008
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49. FOXC1, a New Prognostic Marker in Adult Acute Myeloid Leukemia (AML).

Author

Blanchet, Odile, primary, Galopin, Frederique, primary, Stirewalt, Derek, primary, Hunault-Berger, Mathilde, primary, Beucher, Annaelle, primary, Pogosova-Agadjanyan, Era, primary, Ibricevic, Lejla, primary, Baranger, Laurence, primary, Genevieve, Franck, primary, Zandecki, Marc, primary, Ifrah, Norbert, primary, Radich, Jerald P., primary, and Guardiola, Philippe, primary

Published
2007
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