Epigenome modifications and genomic instability in normal and malignant B cells
Molecular bases of human diseases
Antibody secreting cells are critical effector cells and long-lived sentinels for immune memory. B cell maturation should be tightly regulated to ensure efficient immune response without autoimmunity or immune deficiency. On the transcriptional level, the differentiation of B cells into plasma cells is associated with substantial and coordinated changes in the gene expression profile, which fall into two main categories: the loss of B cell-associated transcripts and the acquisition of plasma cell gene expression program. These changes are tightly guided by two sets of stage-specific transcription factors (TFs) that repress each other: i) B cell TFs (PAX5, BCL6 and BACH2) maintaining the B cell fate and ii) plasma cell TFs (IRF4, BLIMP1 and XBP1) that are required to extinguish the B cell genes and activate the antibody-secreting cell program. Although the role of the complex network of transcription factors involved in plasma cell differentiation has been investigated, the mechanisms regulating key plasma cell differentiation transcription networks remain poorly known. Little is known about the dynamic and hierarchical nuclear architecture in B to plasma cell differentiation and how it could regulate fundamental processes during normal plasma cell differentiation. We aim to characterize and understand the epigenetic, remodeling, structural and architectural changes that affect chromatin during B to plasma cell differentiation. Furthermore, we aim to identify the molecular events involved in tumorigenesis during B to PC differentiation.
Mature B cell malignancies are genetically and clinically heterogeneous diseases. Treatment improvements will come from a better comprehension of tumorigenesis and detailed molecular analyses to develop individualized therapies that take into account their molecular heterogeneity and subclonal evolution.
Our laboratory uses genome data, computing, mathematical modeling and unique cellular models to study mature B cells and plasma cells with a focus on epigenome modifications and genomic instability. These approaches work in tandem with technological advancements to study tumorigenesis and to understand the mechanisms of tumor progression and drug resistance to develop new diagnostic and treatment strategies.
These projects are developed in collaboration with other groups of the IGH together with the departments of biological and clinical hematology of the university hospital of Montpellier. Taking advantage of the link with the laboratory of monitoring innovative therapies (Montpellier University Hospital), dedicated to diagnosis and residual disease monitoring of patients with plasma cell neoplasms, we aim to strongly foster a transformation of basic research into translational and clinical applications.
We created a startup company Diag2Tec to valorize the research activity of the group.
Publications of the team
Editorial: Transcriptional control in normal and malignant B-lymphocytes.
The BLM helicase is a new therapeutic target in multiple myeloma involved in replication stress survival and drug resistance.
Ovejero S, Viziteu E, Dutrieux L, Devin J, Lin YL, Alaterre E, Jourdan M, Basbous J, Requirand G, Robert N, de Boussac H, Seckinger A, Hose D, Vincent L, Herbaux C, Constantinou A, Pasero P, Moreaux J
+ Genetic Instability and Cancer / Maintenance of genome integrity during DNA replication
Targeting the β(2) -adrenergic receptor increases chemosensitivity in multiple myeloma by induction of apoptosis and modulating cancer cell metabolism.
Satilmis H, Verheye E, Vlummens P, Oudaert I, Vandewalle N, Fan R, Knight JM, De Beule N, Ates G, Massie A, Moreaux J, Maes A, De Bruyne E, Vanderkerken K, Menu E, Sloan EK, De Veirman K
miRNA profile at diagnosis predicts treatment outcome in patients with B-chronic lymphocytic leukemia: A FILO study
Inhibition of the Protein Arginine Methyltransferase PRMT5 in High-Risk Multiple Myeloma as a Novel Treatment Approach.
Vlummens P, Verhulst S, De Veirman K, Maes A, Menu E, Moreaux J, De Boussac H, Robert N, De Bruyne E, Hose D, Offner F, Vanderkerken K, Maes K
The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias.
Paolillo R, Boulanger M, Gâtel P, Gabellier L, De Toledo M, Tempé D, Hallal R, Akl D, Moreaux J, Baik H, Gueret E, Recher C, Sarry JE, Cartron G, Piechaczyk M, Bossis G
PIM2 kinase has a pivotal role in plasmablast generation and plasma cell survival, opening up novel treatment options in myeloma.
Haas M, Caron G, Chatonnet F, Manenti S, Alaterre E, Devin J, Delaloy C, Bertolin G, Viel R, Pignarre A, Llamas-Gutierrez F, Marchalot A, Decaux O, Tarte K, Delpy L, Moreaux J, Fest T
Targeting Cellular Iron Homeostasis with Ironomycin in Diffuse Large B-cell Lymphoma.
Devin J, Caneque T, Lin YL, Mondoulet L, Veyrune JL, Abouladze M, Garcia De Paco E, Karmous Gadacha O, Cartron G, Pasero P, Bret C, Rodriguez R, Moreaux J
Angiogenic factors could help us to define patients obtaining complete response with undetectable minimal residual disease in untreated CLL patients treated by FCR: results from the CLL2010FMP, a FILO study.
Gagez AL, Paul F, Alaterre E, Gouilleux-Gruart V, Tuaillon E, Lepretre S, Ternant D, Letestu R, Moreaux J, Cartron G
RNA-Sequencing-Based Transcriptomic Score with Prognostic and Theranostic Values in Multiple Myeloma.
Alaterre E, Vikova V, Kassambara A, Bruyer A, Robert N, Requirand G, Bret C, Herbaux C, Vincent L, Cartron G, Elemento O, Moreaux J
Targeting the methyltransferase SETD8 impairs tumor cell survival and overcomes drug resistance independently of p53 status in multiple myeloma.
Herviou L, Ovejero S, Izard F, Karmous-Gadacha O, Gourzones C, Bellanger C, De Smedt E, Ma A, Vincent L, Cartron G, Jin J, De Bruyne E, Grimaud C, Julien E, Moreaux J
The microenvironment of DLBCL is characterized by noncanonical macrophages recruited by tumor-derived CCL5.
Manfroi B, De Grandis M, Moreaux J, Tabruyn S, Mayol JF, Quintero M, Righini C, Sturm N, Aurrand-Lions M, Huard B
Transcription/Replication Conflicts in Tumorigenesis and Their Potential Role as Novel Therapeutic Targets in Multiple Myeloma.
Dutrieux L, Lin YL, Lutzmann M, Rodriguez R, Cogné M, Pasero P, Moreaux J
G9a/GLP targeting in MM promotes autophagy-associated apoptosis and boosts proteasome inhibitor-mediated cell death.
De Smedt E, Devin J, Muylaert C, Robert N, Requirand G, Vlummens P, Vincent L, Cartron G, Maes K, Moreaux J, De Bruyne E
Immunotherapy perspectives in the new era of B-cell editing.
Ueda N, Cahen M, Danger Y, Moreaux J, Sirac C, Cogné M
Role of Polycomb Complexes in Normal and Malignant Plasma Cells.
Varlet E, Ovejero S, Martinez AM, Cavalli G, Moreaux J
DNA Repair Expression Profiling to Identify High-Risk Cytogenetically Normal Acute Myeloid Leukemia and Define New Therapeutic Targets
Ludovic Gabellier, Caroline Bret, Guillaume Bossis, Guillaume Cartron and Jérôme Moreaux
A Retrospective Comparison of DLI and gDLI for Post-Transplant Treatment.
Lamure S, Paul F, Gagez AL, Delage J, Vincent L, Fegueux N, Sirvent A, Gehlkopf E, Veyrune JL, Yang LZ, Kanouni T, Cacheux V, Moreaux J, Bonafoux B, Cartron G, De Vos J, Ceballos P
Characterization of immortalized human islet stromal cells reveals a MSC-like profile with pancreatic features.
Villard O, Armanet M, Couderc G, Bony C, Moreaux J, Noel D, De Vos J, Klein B, Veyrune JL, Wojtusciszyn A
Kinome expression profiling to target new therapeutic avenues in multiple myeloma
Hugues de Boussac Angélique Bruyer Michel Jourdan Anke Maes Nicolas Robert Claire Gourzones Laure Vincent Anja Seckinger Guillaume Cartron Dirk Hose Elke De Bruyne Alboukadel Kassambara Philippe Pasero Jérôme Moreaux
[CD38 antibodies in multiple myeloma].
Moreaux J
CD38 antibodies in multiple myeloma
Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma.
Maes A, Maes K, Vlummens P, De Raeve H, Devin J, Szablewski V, De Veirman K, Menu E, Moreaux J, Vanderkerken K, De Bruyne E
Treatment may be harmful : mechanisms/preduction/prevention of drug-induced DNA damage and repair in multiple myeloma
Claire Gourzones, Caroline Bret and Jerome Moreaux
Phenotypic Characterization of Diffuse Large B-Cell Lymphoma Cells and Prognostic Impact.
Devin J, Kassambara A, Bruyer A, Moreaux J, Bret C
Phenotype Characterization of Diffuse Large B cell Lymphoma Cells and Prognostic Impact
Julie Devin, Alboukadel Kassambara, Angélique Bruyer, Jérôme Moreaux and Caroline Bret
Prospective target assessment and multimodal prediction of survival for personalized and risk-adapted treatment strategies in multiple myeloma in the GMMG-MM5 multicenter trial.
Hose D, Beck S, Salwender H, Emde M, Bertsch U, Kunz C, Scheid C, Hänel M, Weisel K, Hielscher T, Raab MS, Goldschmidt H, Jauch A, Moreaux J, Seckinger A
The hydroxymethylome of multiple myeloma identifies FAM72D as a 1q21 marker linked to proliferation.
Chatonnet F, Pignarre A, Sérandour AA, Caron G, Avner S, Robert N, Kassambara A, Laurent A, Bizot M, Agirre X, Prosper F, Martin-Subero JI, Moreaux J, Fest T, Salbert G
The anaphase-promoting complex/cyclosome: a new promising target in diffuse large B-cell lymphoma and mantle cell lymphoma.
Maes A, Maes K, De Raeve H, De Smedt E, Vlummens P, Szablewski V, Devin J, Faict S, De Veirman K, Menu E, Offner F, Spaargaren M, Moreaux J, Vanderkerken K, Van Valckenborgh E, De Bruyne E
Antioxidant Defenses Confer Resistance to High Dose Melphalan in Multiple Myeloma Cells
Claire Gourzones, Céline Bellanger, Sylvain Lamure, Ouissem Karmous Gadacha, Elvira Garcia De Paco, Laure Vincent, Guillaume Cartron, Bernard Klein and Jérôme Moreau
EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation
Laurie Herviou, Michel Jourdan, Anne-Marie Martinez, Giacomo Cavalli, Jerome Moreaux
Comprehensive characterization of the mutational landscape in multiple myeloma cell lines reveals potential drivers and pathways associated with tumor progression and drug resistance
Veronika Vikova, Michel Jourdan, Nicolas Robert, Guilhem Requirand, Stéphanie Boireau, Angélique Bruyer, Laure Vincent, Guillaume Cartron, Bernard Klein, Olivier Elemento, Alboukadel Kassambara, Jérôme Moreaux
BrdU incorporation in multiparameter flow cytometry: A new cell cycle assessment approach in multiple myeloma.
Requirand G, Robert N, Boireau S, Vincent L, Seckinger A, Bouhya S, Ceballos P, Cartron G, Hose D, Klein B, Moreaux J
PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs
Laurie Herviou, Alboukadel Kassambara, Stéphanie Boireau, Nicolas Robert, Guilhem Requirand, Carsten Müller-Tidow, Laure Vincent, Anja Seckinger, Hartmut Goldschmidt, Guillaume Cartron, Dirk Hose, Giacomo Cavalli & Jerome Moreaux
Tumor-associated neutrophils correlate with poor prognosis in diffuse large B-cell lymphoma patients.
Manfroi B, Moreaux J, Righini C, Ghiringhelli F, Sturm N, Huard B
Analysis of Global Gene Expression Profiles.
Kassambara A, Moreaux J
An epigenetic regulator-related score (EpiScore) predicts survival in patients with diffuse large B cell lymphoma and identifies patients who may benefit from epigenetic therapy
Vanessa Szablewski, Caroline Bret, Alboukadel Kassambara, Julie Devin, Guillaume Cartron, Valérie Costes-Martineau and Jérôme Moreaux
DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells
Angelique Bruyer, Ken Maes, Laurie Herviou, Alboukadel Kassambara, Anja Seckinger, Guillaume Cartron, Thierry Rème, Nicolas Robert, Guilhem Requirand, Stéphanie Boireau, Carsten Müller-Tidow, Jean-luc Veyrune, Laure Vincent, Salahedine Bouhya, Hartmut Goldschmidt, Karin Vanderkerken, Dirk Hose, Bernard Klein, Elke De Bruyne & Jerome Moreaux
Combined inhibition of two bad prognosis genes: Chk1 and Wee1 as a new therapeutic strategy for Multiple Myeloma [Poster]
Angélique Bruyer, Hugues de Boussac, Thibaut Martin, Alboukadel Kassambara, Nicolas Robert, Hose D, Anja Seckinger, Philippe Pasero, Jérôme Moreaux
Combined inhibition of two bad prognosis genes: Chk1 and Wee1 as a new therapeutic strategy for Multiple Myeloma [Abstract]
Angélique Bruyer, Hugues de Boussac, Thibaut Martin, Alboukadel Kassambara, Nicolas Robert, Hose D, Anja Seckinger, Philippe Pasero, Jérôme Moreaux
CD24, CD27, CD36 and CD302 gene expression for outcome prediction in patients with multiple myeloma
Elina Alaterre, Sebastien Raimbault, Hartmut Goldschmidt, Salahedine Bouhya, Guilhem Requirand, Nicolas Robert, Stéphanie Boireau, Anja Seckinger, Dirk Hose, Bernard Klein and Jérôme Moreaux
Hypoxia favors the generation of human plasma cells
Michel Jourdan, Angélique Bruyer, Alboukadel Kassambara, Bernard Klein & Jérôme Moreaux
Global miRNA expression analysis identifies novel key regulators of plasma cell differentiation and malignant plasma cell
Alboukadel Kassambara, Michel Jourdan, Angelique Bruyer, Nicolas Robert, Veronique Pantesco, Olivier Elemento, Bernard Klein and Jerome Moreaux
Differential effects of lenalidomide during plasma cell differentiation
Michel Jourdan, Maïlys Cren, Peter Schafer, Nicolas Robert, Christophe Duperray, Laure Vincent, Patrice Ceballos, Guillaume Cartron, Jean-François Rossi, Jérôme Moreaux, Rajesh Chopra, Bernard Klein
EZH2 in normal hematopoiesis and hematological malignancies
Laurie Herviou, Giacomo Cavalli, Guillaume Cartron, Bernard Klein and Jérôme Moreaux
GenomicScape : AnEasy-to-Use Web Tool for Gene Expression Data Analysis. Application to Investigate the Molecular Events in the Differentiation of B Cells into Plasma Cells
Alboukadel Kassambara, Thierry Rème, Michel Jourdan, Thierry Fest, Dirk Hose, Karin Tarte, Bernard Klein
Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors
J Moreaux, T Reme, W Leonard, J-L Veyrune, G Requirand, H Goldschmidt, D Hose & B Klein
Nucleotide excision DNA repair pathway as a therapeutic target in patients with high-risk diffuse large B cell lymphoma
Caroline Bret, Bernard Klein and Jérôme Moreaux
Nucleotide excision DNA repair pathway as a therapeutic target in patients with high-risk diffuse large B cell lymphoma
Caroline Bret, Bernard Klein and Jérôme Moreaux
Gene expression-based risk score in diffuse large B-cell lymphoma
Caroline Bret, Bernard Klein, and Jérôme Moreaux
Development of gene expression-based risk score in cytogenetically normal acute myeloid leukemia patients
Elias Bou Samra, Bernard Klein, Thérèse Commes, and Jérôme Moreaux
Development of gene expression based score to predict sensitivity of multiple myeloma cells to DNA methylation
Jérôme Moreaux, Thierry Rème, Wim Leonard, et al.
Characterization of a Transitional Preplasmablast Population in the Process of Human B Cell to Plasma Cell Differentiation
Michel Jourdan, Anouk Caraux, Gersende Caron, Nicolas Robert, Geneviève Fiol, Thierry Rème, Karine Bolloré, Jean-Pierre Vendrell, Simon Le Gallou, Frédéric Mourcin, John De Vos, Alboukadel Kassambara, Christophe Duperray, Dirk Hose, Thierry Fest, Karin Tarte and Bernard Klein
An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization.
Jourdan M, Caraux A, De Vos J, Fiol G, Larroque M, Cognot C, Bret C, Duperray C, Hose D, Klein B
Thèses et hdr
Genomic and epigenomic analyses for the development of precision medicine in multiple myeloma 08/10/2019
Defended by Veronika Vikova on 08-10-2019
Etude de l'implication de mécanismes épigénétiques dans la physiopathologie du myélome multiple et dans la différenciation plasmocytaire normale 13/09/2018
Defended by Laurie Herviou on 13-09-2018
Identification fine des cellules plasmocytaires normales et tumorales dans la moelle osseuse de patients atteints de myélome multiple en cytométrie en flux 03/05/2017
Defended by Elina Alaterre on 03-05-2017
RECQ1 Helicase Involvement in the Resistance to Replication Stress and Chemotherapy in Multiple Myeloma Myélome Multiple 24/11/2015
By Elena Viziteu Defended on 24-11-2015
Doctorant
ITA
