- Inherited Bone Marrow Failure (BMF) syndromes
- Acute Lymphoblastic Leukemia (ALL)
- Acute Myeloid Leukemia (AML)
- Myelodysplastic Syndromes (MDS)
- Myeloid sarcoma
- Leukemia predisposition syndromes
- Pediatric and/or germline mutation-associated disorders
IGAALD
The development of acute leukemia is a multistep process characterized by the acquisition of diverse and cumulative genetic alterations. Our team focuses on the identification and the modelization of new genetic alterations of transcription factors in acute myeloid and lymphoid leukemia. Combined with clinical studies and genetic profiling of leukemia patients, the development in our team of cellular and animal models aims to define and target the biological mechanisms by which these new genetic alterations lead to leukemia development or relapse.
METAML
The team focuses its research on :
- Mitochondrial adaptation
- Metabolic dialogues and heterogeneity
- Autophagy and metabolism
- RNA splicing and metabolism
- Targeted therapy
- Immunotherapy
- Chemotherapy
Scientifiques
IGAALD
- Study of the leukemic stem cell in a B-ALL model; ;
- Study of changes in hematopoiesis linked to a germline mutation of GATA2
METAML
- Cancer stem cells are heterogeneous with regard to their sensitivity to chemotherapy and are not necessarily localized in particular hypoxic bone marrow endosteal zones (Cancer Discov. 2017)
- Cancer stem cells exhibit transient post-chemo phenotypes with signatures of EMT plasticity and inflammatory and stress responses (Cancer Discov. 2017; Cancer Discov. 2020)
- Both mitochondrial OxPHOS and Warburg/glycolysis are implicated in chemoresistance. AML cells have high metabolic capacities and are metabolically flexible especially when challenged by chemotherapeutic drugs (Leukemia. 2013; Cancer Discov. 2017; Cell Metab. 2017)
- Adaptations in mitochondrial dynamics (Nature Com. 2020; Nature Cancer 2021) and lipid flexibility (J Exp Med. 2021) are due to a pleiotropic and Darwinian mechanism of mitochondrial stress response to apoptosis or ferroptosis induced by conventional chemotherapeutics and novel targeted therapies (Cancer Discov. 2020; Nature Cancer 2021; Cancer Discov. 2023)
Médicales
IGAALD
- Impact of germline DDX41 mutations in the progression of AML
- Impact of germline GATA2 mutations in the evolution of AML
- Molecular profile of response to the addition of CCNU in AML in elderly subjects
METAML
- Establishment of a mitochondrial score (mitoscore) by Seahorse and RNA analysis for the management of AML patients
IGAALD
- Fregona V, Bayet M, Bouttier M, Largeaud L, Hamelle C, Jamrog LA, Prade N, Lagarde S, Hebrard S, Luquet I, Mansat-De Mas V, Nolla M, Pasquet M, Didier C, Khamlichi AA, Broccardo C, Delabesse E, Mancini SJC, Gerby B. Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL. J Exp Med. 2024;221(1).
- Largeaud L, Collin M, Monselet N, Vergez F, Fregona V, Larcher L, Hirsch P, Duployez N, Bidet A, Luquet I, Bustamante J, Dufrechou S, Prade N, Nolla M, Hamelle C, Tavitian S, Habib C, Meynier M, Bellanne-Chantelot C, Donadieu J, De Fontbrune FS, Fieschi C, Ferster A, Delhommeau F, Delabesse E, Pasquet M. Somatic genetic alterations predict hematological progression in GATA2 deficiency. Haematologica. 2023;108(6):1515-29.
- Duployez N, Largeaud L, Duchmann M, Kim R, Rieunier J, Lambert J, Bidet A, Larcher L, Lemoine J, Delhommeau F, Hirsch P, Fenwarth L, Kosmider O, Decroocq J, Bouvier A, Le Bris Y, Ochmann M, Santagostino A, Ades L, Fenaux P, Thomas X, Micol JB, Gardin C, Itzykson R, Soulier J, Clappier E, Recher C, Preudhomme C, Pigneux A, Dombret H, Delabesse E, Sebert M. Prognostic impact of DDX41 germline mutations in intensively treated acute myeloid leukemia patients: an ALFA-FILO study. Blood. 2022;140(7):756-68.
- Lafage-Pochitaloff M, Gerby B, Baccini V, Largeaud L, Fregona V, Prade N, Juvin PY, Jamrog L, Bories P, Hebrard S, Lagarde S, Mansat-De Mas V, Dovey OM, Yusa K, Vassiliou GS, Jansen JH, Tekath T, Rombaut D, Ameye G, Barin C, Bidet A, Boudjarane J, Collonge-Rame MA, Gervais C, Ittel A, Lefebvre C, Luquet I, Michaux L, Nadal N, Poirel HA, Radford-Weiss I, Ribourtout B, Richebourg S, Struski S, Terre C, Tigaud I, Penther D, Eclache V, Fontenay M, Broccardo C, Delabesse E. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11. Blood Adv. 2022;6(2):386-98.
- Duployez N, Jamrog LA, Fregona V, Hamelle C, Fenwarth L, Lejeune S, Helevaut N, Geffroy S, Caillault A, Marceau-Renaut A, Poulain S, Roche-Lestienne C, Largeaud L, Prade N, Dufrechou S, Hebrard S, Berthon C, Nelken B, Fernandes J, Villenet C, Figeac M, Gerby B, Delabesse E, Preudhomme C, Broccardo C. Germline PAX5 mutation predisposes to familial B-cell precursor acute lymphoblastic leukemia. Blood. 2021;137(10):1424-8.
- Largeaud L, Cornillet-Lefebvre P, Hamel JF, Dumas PY, Prade N, Dufrechou S, Plenecassagnes J, Luquet I, Blanchet O, Banos A, Bene MC, Bernard M, Bertoli S, Bonmati C, Fornecker LM, Guieze R, Haddaoui L, Hunault M, Ianotto JC, Jourdan E, Ojeda M, Peterlin P, Vey N, Zerazhi H, Yosr H, Mineur A, Cahn JY, Ifrah N, Recher C, Pigneux A, Delabesse E, French Innovative Leukemia O. Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study. Leukemia. 2021;35(5):1291-300.
- Jamrog L, Chemin G, Fregona V, Coster L, Pasquet M, Oudinet C, Rouquie N, Prade N, Lagarde S, Cresson C, Hebrard S, Nguyen Huu NS, Bousquet M, Quelen C, Brousset P, Mancini SJC, Delabesse E, Khamlichi AA, Gerby B, Broccardo C. PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice. Proc Natl Acad Sci U S A. 2018;115(41):10357-62.
- Struski S, Lagarde S, Bories P, Puiseux C, Prade N, Cuccuini W, Pages MP, Bidet A, Gervais C, Lafage-Pochitaloff M, Roche-Lestienne C, Barin C, Penther D, Nadal N, Radford-Weiss I, Collonge-Rame MA, Gaillard B, Mugneret F, Lefebvre C, Bart-Delabesse E, Petit A, Leverger G, Broccardo C, Luquet I, Pasquet M, Delabesse E. NUP98 is rearranged in 3.8% of pediatric AML forming a clinical and molecular homogenous group with a poor prognosis. Leukemia. 2017;31(3):565-72.
- Pasquet M, Bellanne-Chantelot C, Tavitian S, Prade N, Beaupain B, Larochelle O, Petit A, Rohrlich P, Ferrand C, Van Den Neste E, Poirel HA, Lamy T, Ouachee-Chardin M, Mansat-De Mas V, Corre J, Recher C, Plat G, Bachelerie F, Donadieu J, Delabesse E. High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood. 2013;121(5):822-9.
- Ballerini P, Struski S, Cresson C, Prade N, Toujani S, Deswarte C, Dobbelstein S, Petit A, Lapillonne H, Gautier EF, Demur C, Lippert E, Pages P, Mansat-De Mas V, Donadieu J, Huguet F, Dastugue N, Broccardo C, Perot C, Delabesse E. RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation. Leukemia. 2012;26(11):2384-9.
METAML
- 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/EBPα 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. doi: 10.1158/2159-8290.CD-22-0411. Erratum in: Cancer Discov. 2023 Sep 6;13(9):2106. PMID: 37012202.
- Bosc C, Saland E, Bousard A, Gadaud N, Sabatier M, Cognet G, Farge T, Boet E, Gotanègre M, Aroua N, Mouchel PL, Polley N, Larrue C, Kaphan E, Picard M, Sahal A, Jarrou L, Tosolini M, Rambow F, Cabon F, Nicot N, Poillet-Perez L, Wang Y, Su X, Fovez Q, Kluza J, Argüello RJ, Mazzotti C, Avet-Loiseau H, Vergez F, Tamburini J, Fournié JJ, Tiong IS, Wei AH, Kaoma T, Marine JC, Récher C, Stuani L, Joffre C, Sarry JE. Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia. Nat Cancer. 2021 Nov;2(11):1204-1223. doi: 10.1038/s43018-021-00264-y. Epub 2021 Nov 11. PMID: 35122057.
- Stuani L, Sabatier M, Saland E, Cognet G, Poupin N, Bosc C, Castelli FA, Gales L, Turtoi E, Montersino C, Farge T, Boet E, Broin N, Larrue C, Baran N, Cissé MY, Conti M, Loric S, Kaoma T, Hucteau A, Zavoriti A, Sahal A, Mouchel PL, Gotanègre M, Cassan C, Fernando L, Wang F, Hosseini M, Chu-Van E, Le Cam L, Carroll M, Selak MA, Vey N, Castellano R, Fenaille F, Turtoi A, Cazals G, Bories P, Gibon Y, Nicolay B, Ronseaux S, Marszalek JR, Takahashi K, DiNardo CD, Konopleva M, Pancaldi V, Collette Y, Bellvert F, Jourdan F, Linares LK, Récher C, Portais JC, Sarry JE. Mitochondrial metabolism supports resistance to IDH mutant inhibitors in acute myeloid leukemia. J Exp Med. 2021 May 3;218(5):e20200924. doi: 10.1084/jem.20200924. PMID: 33760042; PMCID: PMC7995203.
- Larrue C, Guiraud N, Mouchel PL, Dubois M, Farge T, Gotanègre M, Bosc C, Saland E, Nicolau-Travers ML, Sabatier M, Serhan N, Sahal A, Boet E, Mouche S, Heydt Q, Aroua N, Stuani L, Kaoma T, Angenendt L, Mikesch JH, Schliemann C, Vergez F, Tamburini J, Récher C, Sarry JE. Adrenomedullin-CALCRL axis controls relapse-initiating drug tolerant acute myeloid leukemia cells. Nat Commun. 2021 Jan 18;12(1):422. doi: 10.1038/s41467-020-20717-9. PMID: 33462236; PMCID: PMC7813857.
- Aroua N, Boet E, Ghisi M, Nicolau-Travers ML, Saland E, Gwilliam R, de Toni F, Hosseini M, Mouchel PL, Farge T, Bosc C, Stuani L, Sabatier M, Mazed F, Larrue C, Jarrou L, Gandarillas S, Bardotti M, Picard M, Syrykh C, Laurent C, Gotanègre M, Bonnefoy N, Bellvert F, Portais JC, Nicot N, Azuaje F, Kaoma T, Joffre C, Tamburini J, Récher C, Vergez F, Sarry JE. Extracellular ATP and CD39 Activate cAMP-Mediated Mitochondrial Stress Response to Promote Cytarabine Resistance in Acute Myeloid Leukemia. Cancer Discov. 2020 Oct;10(10):1544-1565. doi: 10.1158/2159-8290.CD-19-1008. Epub 2020 Jul 8. PMID: 32641297.
- Farge T, Saland E, de Toni F, Aroua N, Hosseini M, Perry R, Bosc C, Sugita M, Stuani L, Fraisse M, Scotland S, Larrue C, Boutzen H, Féliu V, Nicolau-Travers ML, Cassant-Sourdy S, Broin N, David M, Serhan N, Sarry A, Tavitian S, Kaoma T, Vallar L, Iacovoni J, Linares LK, Montersino C, Castellano R, Griessinger E, Collette Y, Duchamp O, Barreira Y, Hirsch P, Palama T, Gales L, Delhommeau F, Garmy-Susini BH, Portais JC, Vergez F, Selak M, Danet-Desnoyers G, Carroll M, Récher C, Sarry JE. Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism. Cancer Discov. 2017 Jul;7(7):716-735. doi: 10.1158/2159-8290.CD-16-0441. Epub 2017 Apr 17. PMID: 28416471; PMCID: PMC5501738.
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