Our research project at a glance
Despite a high rate of complete remission after treatment with genotoxic agents, the prognosis is poor in human acute myeloid leukemia (AML). Indeed, 5-year overall survival is about 30 to 40% in patients younger than 60 years old and less than 20% in patients over 60. Front-line chemotherapy is highly effective in ablating leukemic cells, but distant relapses are observed in the majority of patients, characterized by a refractory phase during which no other treatment has shown any efficacy thus far. Relapses are caused by tumor regrowth initiated by resistant leukemic clones (RLCs).
The goal of our team is to understand the causes of the drug resistance for the development of new treatments eradicating RLCs and overcoming patient relapses.
The biology of therapeutic resistance currently represents an active area of research. However, the molecular mechanisms underlying AML chemoresistance are still poorly understood, especially in the in vivo context. Our specific aim is to understand and target the mechanisms involved in the drug resistance in AML.
We primarily focus on the role of the mitochondrial energetic and metabolic flexibility in the drug resistance of AML cells. We also study the interactions with stromal cells, which modulate their therapeutic resistance in the tumoral niche.
Using diverse metabolomic, transcriptomic, pharmacological and functional approaches as well as patient samples and a newly developed AML-engrafted immunodeficient model, we aim to :
- elucidate the stemness and functional heterogeneity of RLCs in response to genotoxics in vivo,
- determine how mitochondrial energy and metabolic networks drive the drug resistance of RLCs in vivo
- and define the role of the energetic symbiosis and metabolic dialogue between the stromal compartment and leukemic blasts in the bone marrow niche.
- Drug resistance
- Patient derived xenograft
- Mitochondria, Energetics
- Catabolic flexibility
- Clonal heterogeneity
- Single cell signature
- Cancer stem cells
- Innovative therapeutics
Labels and networks
Grants and funders
Cancer Discov, 7 (7), pp. 716-735, 2017, ISSN: 2159-8290 (Electronic) 2159-8274 (Linking).
J Exp Med, 213 (4), pp. 483-97, 2016, ISSN: 1540-9538 (Electronic) 0022-1007 (Linking).
Blood, 127 (7), pp. 882-92, 2016, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).
Blood, 126 (11), pp. 1346-56, 2015, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).
Blood Cancer J, 5 , pp. e297, 2015, ISSN: 2044-5385 (Electronic) 2044-5385 (Linking).
Cell Rep, 7 (6), pp. 1815-23, 2014, ISSN: 2211-1247 (Electronic).
Leukemia, 27 (11), pp. 2129-38, 2013, ISSN: 1476-5551 (Electronic) 0887-6924 (Linking).
J Clin Invest, 121 (1), pp. 384-95, 2011, ISSN: 1558-8238 (Electronic) 0021-9738 (Linking).
Haematologica, 96 (12), pp. 1792-8, 2011, ISSN: 1592-8721 (Electronic) 0390-6078 (Linking).
A robust xenotransplantation model for acute myeloid leukemia Journal Article
Leukemia, 23 (11), pp. 2109-17, 2009, ISSN: 1476-5551 (Electronic) 0887-6924 (Linking).