Cell Death, Differentiation, Inflammation and Cancer

Centre Méditerranéen de Médecine Moléculaire C3M /
Centre Méditerranéen de Médecine Moléculaire C3M / UMR INSERM U1065,
Bâtiment ARCHIMED, 151 Rte de St Antoine de Ginestière, BP 23194
06204 Nice Cedex 3 – France - Nice
Site web - auberger@unice.fr -

Research themes

Autophagy is a lysosomal degradation mechanism crucial for the regulation of various physiological processes, including cell death and survival, differentiation, development and immunity. Our team is studying the role of apoptosis and autophagy in the mechanisms of resistance to chemotherapies and the implication of autophagy during hematopoietic cell differentiation. More precisely, we are analyzing how defects in apoptotic and autophagy processes may participate to the development and the progression of myelodysplastic syndroms (MDS), acute myeloid leukemia (AML) and myelomonocytic leukemia (CMML). We are focusing our attention on the role of the anti-apoptotic Bcl-2 family members that are involved in the induction of chimioresistance and leukemogenesis. Of note, we have previously established that Bcl-B plays a crucial role in the regulation of both apoptosis and autophagy and in the pathogenesis of myeloïd and lymphoïd malignancies. In this context, we are also validating, thanks to the use of original nucleoside analogs new strategic therapies aiming either at eliminating tumoral myeloid cells or at reactivating their differentiation. These promising strategies are currently being validated in the clinic in chemotherapy-resistant MDS, AML and CMML patients. This work is supported by several grants from INSERM, the LNCC, the ARC foundation, INCA, FDF and the SATT/Sud-Est.

Descriptive figure


Analogues Nucléosidiques : une stratégie thérapeutique efficace dans les hémopathies myéloides

Publications

– Colosetti P, Puissant A, Robert G, Luciano F, Jacquel A, Gounon P, Cassuto JP, and Auberger P. Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy. 2009. 5, 8-14.

– Puissant, A, Robert, G, Fenouille, N, Luciano, F, Cassuto, JP, Raynaud, S and Auberger, P. Resveratrol promotes autophagic cell death in myelogenous leukemia cells through JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Research. 2010. 70 :1042-1052.

– Puissant, A, Colosetti, P, Robert, G, Cassuto, JP, Raynaud, S and Auberger, P. Cathepsin B release following Imatinib-mediated Lysosomal Membrane Permeabilization triggers BCR-ABL cleavage and elimination of CML cells. Leukemia. 2010. 104:115-124.

– Puissant, A., Robert, G., and Auberger, P. Targeting autophagy to fight hematopoietic malignancies. Cell Cycle. 2010 9: 3470-3478.

– Puissant, A. and Auberger, P. AMPK- and p62/SQSTM1-dependent autophagy mediate resveratrol-induced cell death in chronic myelogenous leukemia. Autophagy, 2010, 6 (5):655-7.

– Puissant, A., Dufies, M., Raynaud, S., Cassuto, J. P., and Auberger, P. Targeting lysosomes to eradicate imatinib-resistant chronic myelogenous leukemia cells. Leukemia, 2010, 24: 1099-1101.

– Cluzeau, T., Robert, G., Puissant, A., Jean-Michel, K., Cassuto, J. P., Raynaud, S., and Auberger, P. Azacitidine- resistant SKM1 myeloid cells are defective for AZA-induced mitochondrial apoptosis and autophagy. Cell Cycle. 2011, 10, 2339-2343.

– Jacquel A, Obba S, Boyer L, Dufies M, Robert G, Gounon P, Lemichez E, Luciano F, Solary E and Auberger P. Autophagy is required for CSF-1-induced macrophagic differentiation and acquisition of phagocytic functions. Blood. 2012, 119 :4527-31.

– Cluzeau T, Robert G, Mounier N, Karsenti JM, Dufies M, Puissant A, Jacquel A, Renneville A, Preudhomme C, Cassuto JP, Raynaud S, Luciano F and Auberger P. BCL2L10 is a predictive factor for resistance to aza in MDS and AML patients. Oncotarget. 2012, 3(4):490-501.

– Auberger P. BCR-ABL/p62/SQSTM1: A cannibal embrace. Blood. 2012, Oct 25; 120(17): 3389-90.

– Jacquel, A, Obba, S and Auberger, P. Autophagy, 2012, 8(7) : 1141-3.

– Puissant, A, Fenouille, N and Auberger, P. When autophagy meets cancer through p62/SQSTM1. Am J Cancer Res. 2012, 2(4) : 397-413.

– Robert G, Gastaldi C, Puissant A, Hamouda A, Jacquel A, Dufies M, Belhacene N, Colosetti P, Reed JC, Auberger P, and Luciano F. The anti-apoptotic Bcl-B protein inhibits BECN1-dependent autophagic cell death. Autophagy. 2012, 8(4).