Team “Innovative Therapies in Myeloid Leukemia and Hematopoietic Stem Cells” CFATG
Team “Innovative Therapies in Myeloid Leukemia and Hematopoietic Stem Cells”

Team: Innovative Therapies in Myeloid Leukemia and Hematopoietic Stem Cells

Team presentation

C3M/INSERM U1065 -Univesité Côte d’Azur
151, Route de Saint-Antoine de Ginestière, BP2 3194, 06204 Nice

Website : http://www.unice.fr/c3m/

Team Leader : Dr. Patrick Auberger, DRCE INSERM, auberger@unice.fr

Team members 2021 :
Dr. Guillaume Robert, CRCN INSERM
Dr. Arnaud Jacquel, CRCN INSERM
Dr. Marie-Laure Arcangeli, CRCN INSERM
Pr. Thomas Cluzeau, PU-PH (Hospitalier)
Pr. Nicolas Mounier, PU-PH (Hospitalier)
Dr. Michael Loschi, Chef de clinique (Hospitalier)
Coline Savy, IE CDD INSERM
Maxence Bourgoin, IE CDD INSERM
Cécile Favreau, IE CDD INSERM
Julie Bianco, IE CDD CHU
Paul Chaintreuil, Doctorant
Emeline Kerreneur, Doctorante


From left to right : Paul Chaintreuil, Julie Bianco, Guillaume Robert, Marie-Laure Arcangeli, Coline Savy, Patrick Auberger, Arnaud Jacquel, Maxence Bourgoin, Cécile Favreau.

Keywords: AML/MDS, Lysosomes, Macrophages, MDSC, REDD1, HSC, Innovative Therapies

Research Topic :
Our research team is integrated in the Mediterranean Center for Molecular Medicine (C3M) in Nice, formerly Inserm U1065. Our work focuses on the genesis, differentiation, and transformation of hematopoietic stem cells with a special emphasis on myeloid cells. Our current research project is articulated around 3 main axes: The first one concerns the role of oxydative stress in the maintenance, the proliferation and engraftment of hematopoietic stem cells. The second one studies the role of caspases and autophagy during monocyte differentiation into macrophages and their subsequent polarization. Finally, our last research axe analyses the involvement of lysosomes and different forms of autophagy in the regulation of myeloid leukemia and the development of MDS into AML.

Figure 1: NB4 cells are stimulated with All-trans Retinoic Acid (ATRA) for 24h. These cells are then lysed in a nitrogen disintegration bomb and the organelles from these cells are purified by ultracentrifugation on sucrose gradient. The recovered fractions are analyzed by western blot to determine the modifications linked to the ATRA treatment. The antibodies shown (right panel) are purity controls for the different organelles.

References :
1. Zerhouni, M.; Martin, A.R.; Furstoss, N.; Gutierrez, V.S.; Jaune, E.; Tekaya, N.; Beranger, G.E.; Abbe, P.; Regazzetti, C.; Amdouni, H.; et al. Dual Covalent Inhibition of PKM and IMPDH Targets Metabolism in Cutaneous Metastatic Melanoma. Cancer Res 2021, 81, 3806–3821, doi:10.1158/0008-5472.CAN-20-2114.
2. Klionsky, D.J.; Abdel-Aziz, A.K.; Abdelfatah, S.; Abdellatif, M.; Abdoli, A.; Abel, S.; Abeliovich, H.; Abildgaard, M.H.; Abudu, Y.P.; Acevedo-Arozena, A.; et al. Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (4th Edition)1. Autophagy 2021, 17, 1–382, doi:10.1080/15548627.2020.1797280.
3. Robert, G.; Jacquel, A.; Auberger, P. Chaperone-Mediated Autophagy and Its Emerging Role in Hematological Malignancies. Cells 2019, 8, E1260, doi:10.3390/cells8101260.
4. Auberger P, Puissant A. Autophagy, a key mechanism of oncogenesis and resistance in leukemia. Blood. 2017 Feb. 2;129(5):547-552. PMID: 27956388.
5. Hamouda, M. A.; Jacquel, A.; Robert, G.; Puissant, A.; Richez, V.; Cassel, R.; Fenouille, N.; Roulland, S.; Gilleron, J.; Griessinger, E.; et al. BCL-B (BCL2L10) Is Overexpressed in Patients Suffering from Multiple Myeloma (MM) and Drives an MM-like Disease in Transgenic Mice. J Exp Med 2016, 213, 1705–1722, doi:10.1084/jem.20150983.
6. Obba, S.; Hizir, Z.; Boyer, L.; Selimoglu-Buet, D.; Pfeifer, A.; Michel, G.; Hamouda, M.-A.; Gonçalvès, D.; Cerezo, M.; Marchetti, S.; et al. The PRKAA1/AMPKα1 Pathway Triggers Autophagy during CSF1-Induced Human Monocyte Differentiation and Is a Potential Target in CMML. Autophagy 2015, 11, 1114–1129, doi:10.1080/15548627.2015.1034406.

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