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Cochin Institute (UMR-1016)

The field of research of the team focus on the study of normal myeloid development, from the hematopoietic stem cell to the mature erythroblast and their pathological counterparts in myelodysplastic syndromes and acute myeloid leukemias, to identify mechanisms of the diseases and therapeutic targets.

Michaela Fontenay
Prof. Michaela Fontenay

Head of Entity

Didier Bouscary
Prof. Didier Bouscary

Head of Entity

Contact

Email : michaela.fontenay@inserm.fr

Institut Cochin
22, rue Méchain
Bâtiment Gustave Roussy
75014 PARIS - France

Website

  • Acute Myeloid Leukemia (AML)
  • Myelodysplastic Syndromes (MDS)

  • RNA biology and regulation by RNA binding proteins in normal hematopoietic stem cell and myelodysplastic syndromes
  • Targeting ferroptosis and mitochondrion metabolism in acute myeloid leukemia
  • (Epi)genetics, transcriptomics and proteogenomics to support outcome prediction models and personalised medicine in myelodysplastic syndromes

 

  • Targeted therapy
  • Immunotherapy
  • Chemotherapy

Scientific

  • Identification of a variant protein of erythroferrone, the erythroid transcriptional repressor of hepcidin produced by the use of an alternative 3’ splice site in SF3B1-mutated myelodysplastic syndrome. This protein variant contributes to increased levels of circulating erythroferrone and systemic hyperferritinemia before any transfusion
  • Identification of synthetic lethal interactions between Ras pathway inhibition and mitochondrial oxidative metabolism
  • First evidence of increased sensitivity to ferroptosis of FLT3-mutated AML cells in response to FLT3 inhibition 
  • First evidence that not all tumour-infiltrating T cells are specific for tumour antigens and that these bystander T CD8 cells may recognize a wide range of epitopes unrelated to cancer

Medical

  • Eradication of leukemic stem cells by venetoclax combination therapy
  • First identification of APR436 as a ferroptosis inducer

  • Sabatier M, Birsen R, Lauture L, Mouche S, Angelino P, Dehairs J, Goupille L, Boussaid I, Heiblig M, Boet E, Sahal A, Saland E, Santos JC, Armengol M, Fernández-Serrano M, Farge T, Cognet G, Simonetta F, Pignon C, Graffeuil A, Mazzotti C, Avet-Loiseau H, Delos O, Bertrand-Michel J, Chedru A, Dembitz V, Gallipoli P, Anstee NS, Loo S, Wei AH, Carroll M, Goubard A, Castellano R, Collette Y, Vergez F, Mansat-De Mas V, Bertoli S, Tavitian S, Picard M, Récher C, Bourges-Abella N, Granat F, Kosmider O, Sujobert P, Colsch B, Joffre C, Stuani L, Swinnen JV, Guillou H, Roué G, Hakim N, Dejean AS, Tsantoulis P, Larrue C, Bouscary D, Tamburini J, Sarry JE. C/EBP? Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress-Induced Ferroptosis in FLT3-Mutant Leukemia. Cancer Discov. 2023 Jul 7;13(7):1720-1747.
  • Dussiau C, Boussaroque A, Gaillard M, Bravetti C, Zaroili L, Knosp C, Friedrich C, Asquier P, Willems L, Quint L, Bouscary D, Fontenay M, Espinasse T, Plesa A, Sujobert P, Gandrillon O, Kosmider O. Hematopoietic differentiation is characterized by a transient peak of entropy at a single-cell level. BMC Biol. 2022 Mar 9;20(1):60.
  • Grenier A, Poulain L, Mondesir J, Jacquel A, Bosc C, Stuani L, Mouche S, Larrue C, Sahal A, Birsen R, Ghesquier V, Decroocq J, Mazed F, Lambert M, Andrianteranagna M, Viollet B, Auberger P, Lane AA, Sujobert P, Bouscary D, Sarry JE, Tamburini J. AMPK-PERK axis represses oxidative metabolism and enhances apoptotic priming of mitochondria in acute myeloid leukemia. Cell Rep. 2022 Jan 4;38(1):110197.
  • Decroocq J, Birsen R, Montersino C, Chaskar P, Mano J, Poulain L, Friedrich C, Alary AS, Guermouche H, Sahal A, Fouquet G, Gotanègre M, Simonetta F, Mouche S, Gestraud P, Lescure A, Del Nery E, Bosc C, Grenier A, Mazed F, Mondesir J, Chapuis N, Ho L, Boughalem A, Lelorc'h M, Gobeaux C, Fontenay M, Recher C, Vey N, Guillé A, Birnbaum D, Hermine O, Radford-Weiss I, Tsantoulis P, Collette Y, Castellano R, Sarry JE, Pasmant E, Bouscary D, Kosmider O, Tamburini J. RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia. Leukemia. 2022 May;36(5):1237-1252.
  • Levavasseur F, Oussous S, Zubaidan T, Kosmider O, Pendino F, Rombaut D, Bouscary D, Fontenay M, Lauret E, Dusanter-Fourt I. FOXP1 regulates oxidative stress, SIRT1 expression, and resistance to chemotherapies in acute myeloid leukemia cells. Blood Adv. 2023 Jul 11;7(13):3265-3275.
  • Grignano E, Cantero-Aguilar L, Tuerdi Z, Chabane T, Vazquez R, Johnson N, Zerbit J, Decroocq J, Birsen R, Fontenay M, Kosmider O, Chapuis N, Bouscary D. Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein. Cell Death Discov. 2023 Mar 17;9(1):97.
  • Bondu S, Alary AS, Lefèvre C, Houy A, Jung G, Lefebvre T, Rombaut D, Boussaid I, Bousta A, Guillonneau F, Perrier P, Alsafadi S, Wassef M, Margueron R, Rousseau A, Droin N, Cagnard N, Kaltenbach S, Winter S, Kubasch AS, Bouscary D, Santini V, Toma A, Hunault M, Stamatoullas A, Gyan E, Cluzeau T, Platzbecker U, Adès L, Puy H, Stern MH, Karim Z, Mayeux P, Nemeth E, Park S, Ganz T, Kautz L, Kosmider O§, Fontenay M§*. A variant erythroferrone disrupts iron homeostasis in SF3B1-mutated myelodysplastic syndrome. Sci Transl Med. 2019 Jul 10;11(500):eaav5467.
  • Vazquez R, Breal C, Zalmai L, Friedrich C, Almire C, Contejean A, Barreau S, Grignano E, Willems L, Deau-Fischer B, Franchi P, Vignon M, Decroocq J, Birsen R, Goldwirt L, Kaltenbach S, Couronne L, Fontenay M, Kosmider O, Bouscary D, Chapuis N. Venetoclax combination therapy induces deep AML remission with eradication of leukemic stem cells and remodeling of clonal haematopoiesis. Blood Cancer J. 2021 Mar 19;11(3):62.
  • Birsen R, Larrue C, Decroocq J, Johnson N, Guiraud N, Gotanegre M, Cantero-Aguilar L, Grignano E, Huynh T, Fontenay M, Kosmider O, Mayeux P, Chapuis N, Sarry JE, Tamburini J, Bouscary D. APR-246 induces early cell death by ferroptosis in acute myeloid leukemia. Haematologica. 2022 Feb 1;107(2):403-416.
  • Simoni Y*, Becht E, Fehlings M, Loh CY, Koo SL, Teng KWW, Yeong JPS, Nahar R, Zhang T, Kared H, Duan K, Ang N, Poidinger M, Lee YY, Larbi A, Khng AJ, Tan E, Fu C, Mathew R, Teo M, Lim WT, Toh CK, Ong BH, Koh T, Hillmer AM, Takano A, Lim TKH, Tan EH, Zhai W, Tan DSW, Tan IB, Newell EW. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018 May;557(7706):575-579.

Research infrastructures

Genomics

Cochin Institute Genomics (DNA-seq, RNA-seq, methylation) platform - GENOM'IC.

 

Proteomics

Cochin Institute Proteomics platform – PROTEOM'IC.

 

Cytometry

Cochin Institute Cytometry (flow cytometry high dimensional, multiparametric, cell sorting) platform – CYBIO.

 

Small animal imaging

Cochin Institute Small animal imaging platform – PIV.

 
Clinical trial Cochin Hospital (AP-HP).
Biological samples  

Various sources

AML

MDS

Cochin Hospital biological resources center.

 
Category Models Pathology Specification Sample type Number of models Genetics characterization
In vitro Human primary cells AML - Diagnosis - -
In vitro Human primary cells AML - Relapse - -
In vitro Human primary cells MDS - Diagnosis - -
In vitro Human primary cells MDS - Evolution - -
In vivo Mouse model AML MLL-AF9 - - -
In vivo Mouse model AML MLL-ENL - - -

Various sources

Cell biobank data

Cell biobank of the laboratory of hematology within the Biological resources center of Cochin hospital (certification NFS96900).

Registry/observatory

Clinical data

Annotated databases of myelodysplastic syndromes.

 

French Registry of Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemias.

 

Partnership research offers

INVESTIGATING THE MECHANISM OF ACTION OF DRUG CANDIDATES FOR THE TREATMENT OF MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA

Partners

Academics

Affiliation

CNRS Inserm Université Paris Cité