TEAM
CARINE JOFFRE / MARGHERITA GHISI

ADAPTAML :

Non-genetic adaptive mechanisms and

therapy resistance in acute myeloid leukemia

The Specifities

of our research axis

Acute myeloid leukemia is a highly aggressive and poor prognosis blood cancer that derives from the accumulation of genetic and epigenetic alterations in hematopoietic progenitor cells. Despite important advances in our understanding of this disease, the vast majority of patients experience disease relapse upon therapy and the 5-year survival rate is only 30%. A deeper mechanistic understanding of AML biology alongside the identification of new molecular and cellular vulnerabilities will be key in order to identify new therapeutic strategies and improve patient outcome.
For many years sequential genetic evolution has been considered as the primary cause of cancer onset and resistance to therapy. However, beside genetic alterations, there is a growing appreciation that non-genetic mechanisms of adaptation and plasticity involving a dynamic dialogue between cancer cells and their microenvironment play a key role both in the tumorigenic process and in the acquisition of resistance to anti-cancer therapies. While our understanding of these mechanisms is still very limited, this emerging field of research may hold the key to acquire a global and deeper understanding of AML biology and provide new tools to treat this cancer.
Propelled by this idea and by our common scientific interests, our research is focused on the non-genetic mechanisms that promote adaptive response and survival of AML cells. More specifically, our work explores the role of autophagy, quiescence and epigenetic/post-transcriptional regulation of gene expression in the context of leukemia progression, therapy resistance and relapse, taking into account the interplay between the leukemic blasts and their microenvironment.
To tackle these questions, we combine clinically relevant in vivo AML models, including patient- and cell line-derived human AML xenografts (PDXs and CLDXs) and transgenic mouse models, with various -omics approaches (bulk and single-cell RNA seq, ATACseq, iCLIP, proteomics, metabolomics) as well as functional genetic and pharmacologic screenings. We envision that our work will lay the groundwork for the rational design of more efficient therapies and improved clinical management for AML patients.

Acute Myeloid Leukemia,

Adaptation,

Hematopoiesis,

Resistance,

Autophagy,

RNA splicing,

microenvironment,

Stem cells,

Quiescence,

 Epigenetics.

RESEARCH PROJECTS

THE TEAM’S
FOCUS

Discover

No Results Found

The page you requested could not be found. Try refining your search, or use the navigation above to locate the post.

Understand

No Results Found

The page you requested could not be found. Try refining your search, or use the navigation above to locate the post.

Participate

No Results Found

The page you requested could not be found. Try refining your search, or use the navigation above to locate the post.

SCIENTIFIC PRODUCTIONS

 

PUBLICATIONS 2024
Larrue, Clement, Sarah Mouche, Paolo Angelino, Maxime Sajot, Rudy Birsen, Olivier Kosmider, Thomas Mckee, et al. “Targeting Ferritinophagy Impairs Quiescent Cancer Stem Cells in Acute Myeloid Leukemia in Vitro and in Vivo Models.” Science Translational Medicine 16, no. 757 (July 24, 2024): eadk1731. https://doi.org/10.1126/scitranslmed.adk1731.
PUBLICATIONS 2023
Courdy, Charly, Loïc Platteeuw, Charlotte Ducau, Isabelle De Araujo, Emeline Boet, Ambrine Sahal, Estelle Saland, et al. “Targeting PP2A-Dependent Autophagy Enhances Sensitivity to Ruxolitinib in JAK2V617F Myeloproliferative Neoplasms.” Blood Cancer Journal 13, no. 1 (July 10, 2023): 106. https://doi.org/10.1038/s41408-023-00875-x.
PUBLICATIONS 2022
PUBLICATIONS 2021
Joffre, Carine, Charlotte Ducau, Laura Poillet-Perez, Charly Courdy, and Véronique Mansat-De Mas. “Autophagy a Close Relative of AML Biology.” Biology 10, no. 6 (June 18, 2021): 552. https://doi.org/10.3390/biology10060552.
Bosc, Claudie, Estelle Saland, Aurélie Bousard, Noémie Gadaud, Marie Sabatier, Guillaume Cognet, Thomas Farge, et al. “Mitochondrial Inhibitors Circumvent Adaptive Resistance to Venetoclax and Cytarabine Combination Therapy in Acute Myeloid Leukemia.” Nature Cancer 2, no. 11 (2021): 1204–23. https://doi.org/10.1038/s43018-021-00264-y.
PUBLICATIONS 2020
Aroua, Nesrine, Emeline Boet, Margherita Ghisi, Marie-Laure Nicolau-Travers, Estelle Saland, Ryan Gwilliam, Fabienne de Toni, et al. “Extracellular ATP and CD39 Activate CAMP-Mediated Mitochondrial Stress Response to Promote Cytarabine Resistance in Acute Myeloid Leukemia.” Cancer Discovery, July 8, 2020, CD-19-1008. https://doi.org/10.1158/2159-8290.CD-19-1008.
Bosc, Claudie, Nicolas Broin, Marjorie Fanjul, Estelle Saland, Thomas Farge, Charly Courdy, Aurélie Batut, et al. “Autophagy Regulates Fatty Acid Availability for Oxidative Phosphorylation through Mitochondria-Endoplasmic Reticulum Contact Sites.” Nature Communications 11, no. 1 (2020): 4056. https://doi.org/10.1038/s41467-020-17882-2.
PUBLICATIONS 2019
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 8, no. 8 (July 16, 2019): 39. https://doi.org/10.1038/s41389-019-0148-9.
PUBLICATIONS 2018
Heydt, Q., C. Larrue, E. Saland, S. Bertoli, J.-E. Sarry, A. Besson, S. Manenti, C. Joffre, and V. Mansat-De Mas. “Oncogenic FLT3-ITD Supports Autophagy via ATF4 in Acute Myeloid Leukemia.” Oncogene 37, no. 6 (08 2018): 787–97. https://doi.org/10.1038/onc.2017.376.

TEAM MEMBERS

 

TEAM MEMBERS

 

Clément Larrue
Chercheur Post-Doctorant / Post-Doc researcher
Manon Faivre
Doctorant / PhD student
Constance Manso
Ingénieur de laboratoire / laboratory engineer
Maxime Sajot
Doctorant / PhD student
Anaïs Grignon
Doctorant / PhD student
Alexandre Boudet
Ingénieur de laboratoire / laboratory engineer
Loïc Platteeuw
Doctorant / PhD student
François Vergez
Clinicien Chercheur / Researcher hospital practitioner
Margaux Oberling
Doctorant / PhD student
Mathieu Landry
Ingénieur de laboratoire / laboratory engineer
Véronique DE MAS
Clinicien Chercheur / Researcher hospital practitioner
Margherita Ghisi
Chercheur statutaire / permanent scientist
Carine Joffre
Chercheur statutaire / permanent scientist
Latifa Jarrou
Technicien de laboratoire / Laboratory Technician
Charlotte Ducau
Doctorant / PhD student
Estelle Saland
Ingénieur de laboratoire / laboratory engineer
Poillet Laura
Chercheur statutaire / permanent scientist

PARTERNSHIPS & FUNDING

 

Centre de Recherches en Cancérologie de Toulouse

Toulouse Cancer Research Center (Oncopole)

Toulouse - FR

Contact us

+33 5 82 74 15 75

Contact us

Want to join
the CRCT team ?

Join-us

Pin It on Pinterest