- Acquired Bone Marrow Failure (BMF) syndromes
- Acute Lymphoblastic Leukemia (ALL)
- Acute Myeloid Leukemia (AML)
- Myelodysplastic Syndromes (MDS)
- Leukemia predisposition syndromes
Our main research themes are leukemia oncogenesis and targeted therapies, preclinical models; bone marrow failure/aplasia and leukemia predisposition; and treatment resistance. Our studies link several of these areas and have frequent implications for translational research, in collaboration with clinical research groups.
Research groups
- Genome and cancer – Team leaders: Prof. Jean Soulier and Prof. Emmanuelle Clappier
Understanding of clonal evolution drivers, tumor progression and relapse in human acute leukemia. Studies focus on two human diseases prone to step-wise tumor progression, from preleukemia to leukemia and from leukemia to relapse, Fanconi anemia (FA) and other bone marrow failures (Prof. Jean Soulier) and acute lymphoblastic leukemia (ALL, Prof. Emmanuelle Clappier).
- Molecular mechanisms of acute myeloid leukemia development - Team leader: Dr. Alexandre Puissant; Prof. Raphaël Itzykson
Comprehensive approach to decipher altered cellular responses of leukemic cells using large-scale screening strategies, functional genomics and proteomics applied to pre-clinical mouse models.
- Molecular pathology – Team leader: Prof. Hugues de Thé
Acute Promyelocytic Leukaemia, APL, is a simple form of cancer driven by the PML/RARA fusion protein. PML/RARA is a transcriptional repressor that inhibits myeloid differentiation and enhances the survival and proliferation of early myeloid progenitors. Current work on this disease focuses on exploring the basis of APL initiation through deregulated retinoic acid signaling.
A major new research theme of the team is the ultra-early response to chemotherapy in AML.
- Identification and targeting of extrinsic regulators of myeloid malignancies – Team leaders : Dr. Lina Benajiba and Dr. Camille Lobry
Application of cutting edge descriptive and functional large-scale technologies to physiopathologically relevant AML models, for a better understanding of the mechanisms that define myeloid oncogenesis path within the bone marrow, in order to therapeutically leverage environment-driven clonal plasticity to prevent AML development and/or persistence.
- Targeted therapy
- Immunotherapy
- Precision medicine
- Chemotherapy
- Identification of new oncogenic subtypes of ALL. Clonal evolution in xenografts (Prof. Emmanuel Clappier)
- French reference laboratory for Fanconi anemia. Pathophysiology of hematopoietic failure and secondary leukemogenesis. (Prof. Jean Soulier)
- Understanding the basis of leukemic transformation by the PML/RARA fusion protein and arsenic or retinoic acid therapy (Prof. Hugues de Thé)
- Deciphering the biochemical assembly and normal function(s) of PML nuclear bodies (Prof. Hugues de Thé)
- Sebert M, Gachet S, Leblanc T, Rousseau A, Bluteau O, Kim R, Ben Abdelali R, Sicre de Fontbrune F, Maillard L, Fedronie C, Murigneux V, Bellenger L, Naouar N, Quentin S, Hernandez L, Vasquez N, Da Costa M, Prata PH, Larcher L, de Tersant M, Duchmann M, Raimbault A, Trimoreau F, Fenneteau O, Cuccuini W, Gachard N, Auger N, Tueur G, Blanluet M, Gazin C, Souyri M, Langa Vives F, Mendez-Bermudez A, Lapillonne H, Lengline E, Raffoux E, Fenaux P, Adès L, Forcade E, Jubert C, Domenech C, Strullu M, Bruno B, Buchbinder N, Thomas C, Petit A, Leverger G, Michel G, Cavazzana M, Gluckman E, Bertrand Y, Boissel N, Baruchel A, Dalle JH, Clappier E, Gilson E, Deriano L, Chevret S, Sigaux F, Socié G, Stoppa-Lyonnet D, de Thé H, Antoniewski C, Bluteau D, Peffault de Latour R, Soulier J. Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia. Cell Stem Cell. 2023 Feb 2;30(2):153-170.e9.
- Bluteau O, Sebert M, Leblanc T, Peffault de Latour R, Quentin S, Lainey E, Hernandez L, Dalle JH, Sicre de Fontbrune F, Lengline E, Itzykson R, Clappier E, Boissel N, Vasquez N, Da Costa M, Masliah-Planchon J, Cuccuini W, Raimbault A, De Jaegere L, Adès L, Fenaux P, Maury S, Schmitt C, Muller M, Domenech C, Blin N, Bruno B, Pellier I, Hunault M, Blanche S, Petit A, Leverger G, Michel G, Bertrand Y, Baruchel A, Socié G, Soulier J. A landscape of germ line mutations in a cohort of inherited bone marrow failure patients. Blood. 2018 Feb 15;131(7):717-732.
- Kim R, Bergugnat H, Larcher L, Duchmann M, Passet M, Gachet S, Cuccuini W, Lafage-Pochitaloff M, Pastoret C, Grardel N, Asnafi V, Schäfer BW, Delabesse E, Itzykson R, Adès L, Hicheri Y, Chalandon Y, Graux C, Chevallier P, Hunault M, Leguay T, Huguet F, Lhéritier V, Dombret H, Soulier J, Rousselot P, Boissel N, Clappier E. Adult Low-Hypodiploid Acute Lymphoblastic Leukemia Emerges from Preleukemic TP53-Mutant Clonal Hematopoiesis. Blood Cancer Discov. 2023 Mar 1;4(2):134-149.
- Kim R, Bergugnat H, Pastoret C, Pasquier F, Raffoux E, Larcher L, Passet M, Grardel N, Delabesse E, Kubetzko S, Caye-Eude A, Meyer C, Marschalek R, Lafage-Pochitaloff M, Thiebaut-Bertrand A, Balsat M, Escoffre-Barbe M, Blum S, Baumann M, Banos A, Straetmans N, Gallego-Hernanz MP, Chalandon Y, Graux C, Soulier J, Leguay T, Hunault M, Huguet F, Lheritier V, Dombret H, Boissel N, Clappier E. Genetic alterations and MRD refine risk assessment within KMT2A-rearranged B-cell precursor ALL in adult: a GRAALL study. Blood. 2023 Aug 18:blood.2023021501.
- Itzykson R, Santini V, Thepot S, Ades L, Chaffaut C, Giagounidis A, Morabito M, Droin N, Lübbert M, Sapena R, Nimubona S, Goasguen J, Wattel E, Zini G, Torregrosa Diaz JM, Germing U, Pelizzari AM, Park S, Jaekel N, Metzgeroth G, Onida F, Navarro R, Patriarca A, Stamatoullas A, Götze K, Puttrich M, Mossuto S, Solary E, Gloaguen S, Chevret S, Chermat F, Platzbecker U, Fenaux P. Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network. Journal of Clinical Oncology. 2022 Dec 1:JCO2200437.
- Lin KH, Rutter JC, Xie A, Killarney ST, Vaganay C, Benaksas C, Ling F, Sodaro G, Meslin PA, Bassil CF, Fenouille N, Hoj J, Washart R, Ang HX, Cerda-Smith C, Chaintreuil P, Jacquel A, Auberger P, Forget A, Itzykson R, Lu M, Lin J, Pierobon M, Sheng Z, Li X, Chilkoti A, Owzar K, Rizzieri DA, Pardee TS, Benajiba L, Petricoin E, Puissant A*, Wood KC*. P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia. Nature Cancer. 2022 Jul;3(7):837-851.
- Pardieu B, Pasanisi J, Ling F, Dal Bello R, Penneroux J, Su A, Joudinaud R, Chat L, Wu HC, Duchmann M, Sodaro G, Chauvel C, Castelli FA, Vasseur L, Pacchiardi K, Belloucif Y, Laiguillon MC, Meduri E, Vaganay C, Alexe G, Berrou J, Benaksas C, Forget A, Braun T, Gardin C, Raffoux E, Clappier E, Adès L, de Thé H, Fenaille F, Huntly BJ, Stegmaier K, Dombret H, Fenouille N, Lobry C, Puissant A*, Itzykson R*. Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia. Leukemia. 2022 Jun;36(6):1585-1595.
- Ellegast JM, Alexe G, Hamze A, Lin S, Uckelmann HJ, Rauch PJ, Pimkin M, Ross LS, Dharia NV, Robichaud AL, Conway AS, Khalid D, Perry JA, Wunderlich M, Benajiba L, Pikman Y, Nabet B, Gray NS, Orkin SH, Stegmaier K. Unleashing Cell-Intrinsic Inflammation as a Strategy to Kill AML Blasts. Cancer Discov. 2022 Jul 6;12(7):1760-1781. doi: 10.1158/2159-8290.CD-21-0956. PMID: 35405016; PMCID: PMC9308469.
- Benajiba L, Kiladjian JJ. The challenge of targets and drug discovery using large-scale screening approaches in onco-hematology. Therapie. 2022 Mar-Apr;77(2):151-155.
