Search

Your search keyword '"Sarry, J. E."' showing total 2 results
Start Over Author "Sarry, J. E." Database OpenAIRE
2 results on '"Sarry, J. E."'

1. Oncogenic FLT3-ITD supports autophagy via ATF4 in acute myeloid leukemia

Author

Heydt, Q, Larrue, C., Saland, E, Bertoli, S., Sarry, J-E, Besson, A., Manenti, S., Joffre, C, Mansat-De Mas, V, Cités, Territoires, Environnement et Sociétés (CITERES), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Politecnico di Milano [Milan] (POLIMI), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), and Centre National de la Recherche Scientifique (CNRS)-Université de Tours

Subjects
[SDV]Life Sciences [q-bio], hemic and immune systems, Mice, SCID, Activating Transcription Factor 4, Xenograft Model Antitumor Assays, Leukemia, Myeloid, Acute, Mice, fluids and secretions, fms-Like Tyrosine Kinase 3, Drug Resistance, Neoplasm, Mice, Inbred NOD, Tandem Repeat Sequences, hemic and lymphatic diseases, Mutation, embryonic structures, Autophagy, Biomarkers, Tumor, Tumor Cells, Cultured, Animals, Humans, Original Article, Protein Kinase Inhibitors, Cell Proliferation
Abstract

International audience; In acute myeloid leukemia (AML), internal tandem duplication mutations in the FLT3 tyrosine kinase receptor (FLT3-ITD) account for up to 25% of cases and are associated with a poor outcome. In order to better target this AML subtype, a comprehensive view of how FLT3-ITD impacts AML cell biology is required. Here, we found that FLT3-ITD expression increased basal autophagy in AML cells, and that both pharmacological and genetic inhibition of the receptor reduced autophagy in primary AML samples and cell lines. Conditional expression of shRNAs against key autophagy proteins demonstrated that autophagy is required for AML cell proliferation in vitro and for leukemic cells survival in a mouse model of xenograft. Importantly, autophagy inhibition also overcame FLT3 inhibitor resistance both in vitro and in vivo. The transcription factor ATF4 was identified as an essential actor of FLT3-ITD-induced autophagy. Cellular levels of ATF4 were highly dependent on FLT3-ITD activity, and downregulation of ATF4 inhibited autophagy-dependent AML cell proliferation and improved overall mouse survival similarly to autophagy inhibition. These results suggest that targeting autophagy or ATF4 in patients expressing FLT3 mutations may represent a novel promising and innovative therapeutic strategy for AML.

Published
2018

2. A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

Author

Saland, E, Boutzen, H, Castellano, R, Pouyet, L, Griessinger, E, Larrue, C, de Toni, F, Scotland, S, David, Mathieu, Danet-Desnoyers, G, Vergez, F, Barreira, Y, Collette, Yves, Récher, C, Sarry, J-E, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IUT de Tarbes, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Service d'Expérimentation Animale, UMS006, CHU Toulouse [Toulouse], Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT), 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), University of Pennsylvania-University of Pennsylvania, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), and HAL AMU, Administrateur

Subjects
BUSULFAN, ENGRAFTMENT, [SDV.CAN] Life Sciences [q-bio]/Cancer, NOD/SCID MICE, TRANSPLANTATION, hemic and lymphatic diseases, IMMUNODEFICIENT MICE, CELLS, [SDV.CAN]Life Sciences [q-bio]/Cancer, HEMATOPOIESIS, neoplasms, IRRADIATION
Abstract

International audience; Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2R gamma(null)(c) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results