{"id":43011,"date":"2021-12-01T09:29:57","date_gmt":"2021-12-01T08:29:57","guid":{"rendered":"https:\/\/www.crct-inserm.fr\/?page_id=43011"},"modified":"2024-04-09T09:55:07","modified_gmt":"2024-04-09T07:55:07","slug":"metaml_en","status":"publish","type":"page","link":"https:\/\/www.crct-inserm.fr\/en\/metaml_en\/","title":{"rendered":"METAML_en"},"content":{"rendered":"

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TEAM
Jean-EMMANUEL SARRY \/ CARINE JOFFRE<\/h1>\n

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METAML : <\/span><\/strong><\/h2>\n

Metabolism and Therapeutic Resistance In
Acute Myeloid Leukemia<\/strong><\/h2>\n

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The Toulouse Cancer Laboratory of Excellence is a project that aims to understand the genetic and non-genetic mechanisms of resistance and relapse in cancer.<\/p>\n

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the specifities<\/strong><\/h2>\n

of our research axis<\/h2>\n

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Acute Myeloid Leukemia<\/strong> (AML) is a heterogeneous group of hematological malignancies resulting from the transformation of hematopoietic progenitors. Therapeutic resistance is the major reason of recurrence in AML patients and represents the main consequence of their unfavorable prognosis. The METAML team has shown that this resistance is initiated by cells whose mitochondria have a very high energy and oxidative activity (“OxPHOS”) after conventional chemotherapy but also after newly approved targeted therapies. We also demonstrated that this high mitochondrial activity is due to a metabolic adaptation set up by AML cells in response to mitochondrial stresses induced by the treatments. This leads to an increase in catabolic, energetic and reactive oxygen species (ROS) detoxification capacities, to a high flexibility to use different nutrients and to a greater dependence on mitochondrial NADH dehydrogenases (in particular NADH dehydrogenase of the respiratory chain complex I) Our studies have led to the filing of several patents on new molecular targets (e.g. CD39, CALCRL, ADM) whose inhibition allows sensitization of chemotherapy-resistant cells. More recently, our research has also led us to study the role of metabolic dialogue within the tumor and the host (JE. Sarry), transcriptional regulation and RNA splicing (M. Ghisi), as well as leukemic and host autophagy (C. Joffre) in the adaptive and metabolic mechanisms of therapeutic resistance. All this work is done in a strong preclinical (mouse and xenograft models with CREFRE; diets with ENVT, F. Granat) and clinical context in AML patients (S. Bertoli, V. DeMas, O. Rauzy, C. R\u00e9cher, F. Vergez).<\/p>\n

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Acute myeloid leukemia<\/p>\n

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Metabolism and mitochondria<\/p>\n

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Therapeutic resistance<\/p>\n

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Oxidative stress<\/p>\n

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Metabolic adaptation<\/p>\n

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Leukemic microenvironment<\/p>\n

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Tumor heterogeneity<\/p>\n

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Transcriptional and post-transcriptional regulation<\/p>\n

[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”1_4,1_4,1_4,1_4″ _builder_version=”4.16″ _module_preset=”default” custom_margin=”-30px|auto|-31px|auto||” global_colors_info=”{}”][et_pb_column type=”1_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” text_font=”Open Sans|700|||||||” text_orientation=”center” custom_margin=”||15px||false|false” custom_padding=”15px||15px||false|false” border_color_bottom=”#F19532″ border_width_left=”5px” border_color_left=”#F19532″ global_colors_info=”{}”]<\/p>\n

Autophagy<\/p>\n

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Signaling<\/p>\n

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RESEARCH PROJECTS<\/strong><\/h2>\n

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THE TEAM’S
<\/strong>FOCUS<\/h2>\n

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Discover<\/h4>\n

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Understand<\/h4>\n

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Participate<\/h4>\n

[\/et_pb_text][et_pb_post_slider posts_number=”5″ include_categories=”1321,1289″ show_arrows=”off” use_manual_excerpt=”off” excerpt_length=”0″ show_meta=”off” image_placement=”top” use_bg_overlay=”off” use_text_overlay=”off” dot_nav_custom_color=”#5EC7ED” disabled_on=”off|off|off” _builder_version=”4.21.0″ _module_preset=”default” header_font=”Open Sans|600|||||||” header_text_color=”#5EC7ED” header_font_size=”20px” header_line_height=”1.2em” body_font=”Open Sans||||||||” body_text_align=”left” body_text_color=”#505659″ body_font_size=”18px” background_color=”#FFFFFF” custom_button=”on” button_text_size=”18px” button_bg_color=”#5EC7ED” button_border_width=”0px” button_border_radius=”0px” button_use_icon=”off” button_alignment=”center” button_custom_margin=”20px||0px||false|false” button_custom_padding=”10px|50px|10px|50px|true|true” custom_padding=”0px|||||” header_font_size_tablet=”” header_font_size_phone=”22px” header_font_size_last_edited=”on|phone” body_font_size_tablet=”” body_font_size_phone=”18px” body_font_size_last_edited=”on|phone” border_width_bottom_image=”15px” border_color_bottom_image=”#ffffff” text_shadow_style=”preset4″ text_shadow_vertical_length=”0em” global_colors_info=”{}”][\/et_pb_post_slider][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”448e09ae-9652-4ead-bc5f-152c7adf1202″ global_colors_info=”{}”]<\/p>\n

live<\/strong><\/h2>\n

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\n\t\n \n
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\n Sarry Lab<\/span>\n <\/span>\n Suivre<\/span>\n \n <\/path><\/svg>1,921<\/span>\n <\/path><\/svg>759<\/span>\n <\/span>\n <\/p>\n

\n Dream bigger, anything is possible!\nDriving scientific discovery through collaboration... <\/p>\n <\/div>\n

\n
\n <\/path><\/svg> <\/div>\n \"jeansarry\"\n <\/div>\n <\/a>\n<\/div>\n\n
\n \n
\n\n
\n <\/path><\/svg>Retweeter sur Twitter<\/span><\/a>\n Sarry Lab Retweet\u00e9<\/a>\n<\/div>\n\n
\n
\n \n \"stephxie;\n <\/a>\n \n Stephanie Xie<\/a>\n @stephxie<\/a>\n \n \t\t ·<\/span>\n\t
\n 9 Sep 1700645606950101014<\/span><\/a>\n <\/div>\n <\/div>\n
\n <\/path><\/svg> <\/div>\n <\/div>\n\n
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Important implications of sphingolipids, mitochondria to HSC function and by extension into LSC function. Esp taking into consideration of the p38-CD36-ROS-beta oxidation axis. @RushworthLab @jeansarry @CraigTJordanLab @CLJonesLab<\/p>\n\t\t\t\t\t\t\n \n\t \n \n <\/div>\n \n\t\n

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SCIENTIFIC PRODUCTIONS<\/strong><\/h2>\n

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Grenier, Adrien, Laury Poulain, Johanna Mondesir, Arnaud Jacquel, Claudie Bosc, Lucille Stuani, Sarah Mouche, et al. “AMPK-PERK Axis Represses Oxidative Metabolism and Enhances Apoptotic Priming of Mitochondria in Acute Myeloid Leukemia.” Cell Reports<\/i> 38, no. 1 (January 4, 2022): 110197. https:\/\/doi.org\/10.1016\/j.celrep.2021.110197<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\n

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Chateauvieux, Sébastien, Anthoula Gaigneaux, Déborah Gérard, Marion Orsini, Franck Morceau, Barbora Orlikova-Boyer, Thomas Farge, et al. “Inflammation Regulates Long Non-Coding RNA-PTTG1-1:1 in Myeloid Leukemia.” Haematologica<\/i>, October 3, 2019. https:\/\/doi.org\/10.3324\/haematol.2019.217281<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Largeaud, Laetitia, Sarah Bertoli, Emilie Bérard, Stéphanie Dufrechou, Naïs Prade, Noémie Gadaud, Suzanne Tavitian, et al. “Outcome of Relapsed\/Refractory AML Patients with IDH1R132 Mutations in Real Life before the Era of IDH1 Inhibitors.” Leukemia & Lymphoma<\/i>, September 30, 2019, 1–4. https:\/\/doi.org\/10.1080\/10428194.2019.1668937<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Berger, Eloïse, Cyrille Delpierre, Fabien Despas, Sarah Bertoli, Emilie Bérard, Oriane Bombarde, Pierre Bories, et al. “Are Social Inequalities in Acute Myeloid Leukemia Survival Explained by Differences in Treatment Utilization? Results from a French Longitudinal Observational Study among Older Patients.” BMC Cancer<\/i> 19, no. 1 (September 5, 2019): 883. https:\/\/doi.org\/10.1186\/s12885-019-6093-3<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Hosseini, Mohsen, Hamid Rezvani, Nesrine Aroua, Claudie Bosc, Thomas Farge, Estelle Saland, Véronique Guyonnet-Dupérat, et al. “Targeting Myeloperoxidase Disrupts Mitochondrial Redox Balance and Overcomes Cytarabine Resistance in Human Acute Myeloid Leukemia.” Cancer Research<\/i>, July 29, 2019. https:\/\/doi.org\/10.1158\/0008-5472.CAN-19-0515<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Stuani, Lucille, and Jean-Emmanuel Sarry. “Help from Outside: Cysteine to Survive in AML.” Blood<\/i> 134, no. 4 (July 25, 2019): 336–38. https:\/\/doi.org\/10.1182\/blood.2019001580<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Stuani, Lucille, Marie Sabatier, and Jean-Emmanuel Sarry. “Exploiting Metabolic Vulnerabilities for Personalized Therapy in Acute Myeloid Leukemia.” BMC Biology<\/i> 17, no. 1 (July 18, 2019): 57. https:\/\/doi.org\/10.1186\/s12915-019-0670-4<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Larrue, Clément, Quentin Heydt, Estelle Saland, Héléna Boutzen, Tony Kaoma, Jean-Emmanuel Sarry, Carine Joffre, and Christian Récher. “Oncogenic KIT Mutations Induce STAT3-Dependent Autophagy to Support Cell Proliferation in Acute Myeloid Leukemia.” Oncogenesis<\/i> 8, no. 8 (July 16, 2019): 39. https:\/\/doi.org\/10.1038\/s41389-019-0148-9<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Boutin, Laetitia, Pierre Arnautou, Aurélie Trignol, Amandine Ségot, Thomas Farge, Christophe Desterke, Sabrina Soave, et al. “Mesenchymal Stromal Cells Confer Chemoresistance to Myeloid Leukemia Blasts through Side Population Functionality and ABC Transporter Activation.” Haematologica<\/i>, July 9, 2019. https:\/\/doi.org\/10.3324\/haematol.2018.214379<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Bertoli, Sarah, Suzanne Tavitian, Pierre Bories, Isabelle Luquet, Eric Delabesse, Thibault Comont, Audrey Sarry, Françoise Huguet, Emilie Bérard, and Christian Récher. “Outcome of Patients Aged 60-75 Years with Newly Diagnosed Secondary Acute Myeloid Leukemia: A Single-Institution Experience.” Cancer Medicine<\/i>, June 7, 2019. https:\/\/doi.org\/10.1002\/cam4.2020<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Largeaud, Laetitia, Emilie Bérard, Sarah Bertoli, Stéphanie Dufrechou, Naïs Prade, Noémie Gadaud, Suzanne Tavitian, et al. “Outcome of AML Patients with IDH2 Mutations in Real World before the Era of IDH2 Inhibitors.” Leukemia Research<\/i> 81 (April 27, 2019): 82–87. https:\/\/doi.org\/10.1016\/j.leukres.2019.04.010<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Bertoli, Sarah, Etienne Paubelle, Emilie Bérard, Estelle Saland, Xavier Thomas, Suzanne Tavitian, Marie-Virginie Larcher, et al. “Ferritin Heavy\/Light Chain (FTH1\/FTL) Expression, Serum Ferritin Levels, and Their Functional as Well as Prognostic Roles in Acute Myeloid Leukemia.” European Journal of Haematology<\/i> 102, no. 2 (February 2019): 131–42. https:\/\/doi.org\/10.1111\/ejh.13183<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\t\t\t\t
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Bertoli, Sarah, Suzanne Tavitian, Emilie Berard, Noemie Gadaud, Isabelle Luquet, Anne Huynh, Audrey Sarry, Françoise Huguet, and Christian Récher. “Outcome of Relapsed or Refractory Acute Myeloid Leukemia Treated with Intensive Salvage Chemotherapy in Real Life in Comparison to Intermediate Dose Cytarabine in Phase 3 Studies.” Leukemia & Lymphoma<\/i> 60, no. 1 (2019): 238–41. https:\/\/doi.org\/10.1080\/10428194.2018.1464156<\/a>.<\/div>\n<\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n\n\n

[\/et_pb_toggle][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”448e09ae-9652-4ead-bc5f-152c7adf1202″ global_colors_info=”{}”]<\/p>\n

TEAM MEMBERS<\/strong><\/h2>\n

[\/et_pb_text][et_pb_divider color=”#F19532″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][\/et_pb_divider][\/et_pb_column][\/et_pb_row][et_pb_row _builder_version=”4.16″ _module_preset=”default” max_width=”none” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”][et_pb_text _builder_version=”4.16″ _module_preset=”default” global_colors_info=”{}”]<\/p>\n

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\"\"<\/a><\/div>\n
Manon FAIVRE<\/a><\/div>\n
Master \/ Master student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Yann Aubert<\/a><\/div>\n
Chercheur Post-Doctorant \/ Post-Doc researcher<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Constance MANSO<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Maxime Sajot<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Ana\u00efs Grignon<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Alexandre Boudet<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Lo\u00efc Platteeuw<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Nathaniel Polley<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Odile Rauzy<\/a><\/div>\n
Clinicien Chercheur \/ Researcher hospital practitioner<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Fran\u00e7ois Vergez<\/a><\/div>\n
Clinicien Chercheur \/ Researcher hospital practitioner<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Jean-Emmanuel Sarry<\/a><\/div>\n
Chercheur statutaire \/ permanent scientist<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Margaux Oberling<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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\"\"<\/a><\/div>\n
Mathieu Landry<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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V\u00e9ronique DE MAS<\/a><\/div>\n
Clinicien Chercheur \/ Researcher hospital practitioner<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Margherita Ghisi<\/a><\/div>\n
Chercheur statutaire \/ permanent scientist<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Emeline Boet<\/a><\/div>\n
Chercheur Post-Doctorant \/ Post-Doc researcher<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Nathan Guiraud<\/a><\/div>\n
Ing\u00e9nieur de laboratoire \/ laboratory engineer<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Carine Joffre<\/a><\/div>\n
Chercheur statutaire \/ permanent scientist<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Laura Lauture<\/a><\/div>\n
Doctorant \/ PhD student<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n
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Latifa Jarrou<\/a><\/div>\n
Technicien de laboratoire \/ Laboratory Technician<\/div><\/div>\n<\/div><\/div><\/div> <\/div>\n <\/div>\n<\/div><\/div>\n\n
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