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.

Elina ALATERRE
Researcher

0467335708
Caroline BRET
Researcher

Hugues DE BOUSSAC
Researcher

0467337903
Charles HERBAUX
Researcher

0467330490
Malik LUTZMANN
Researcher

Jerome MOREAUX
Researcher

0467337903
Alizee STEER
Researcher

0434359811
Morgane Thomas
Morgane THOMAS
Researcher

0467337903
Djamila Chemlal
Djamila CHEMLAL
PhD Student

Laure DUTRIEUX
PhD Student

0467335708
Emmanuel VARLET
PhD Student

0467335708
Matthieu ABOULADZE
RESPONSABLE TECHNIQUE DE LA COLLECTION HEMODIAG CRB
ITA

0467335706
Elvira GARCIA DE PACO
ITA

0467335706
Antoine Guillemin
Antoine GUILLEMIN
Ingénieur en analyses de données biologiques
ITA

0467337903
Valentin Jacquier
Valentin JACQUIER
Ingénieur en Biologie
ITA

Ouissem KARMOUS-GADACHA
ITA

0467335706
Sara OVEJERO MERINO
ITA

0467335708
Guilhem REQUIRAND
ITA

0467335707
Nicolas ROBERT
ITA

0467330490
Miss Leriem Zellagui
Miss Leriem ZELLAGUI
ITA

0467337903
Salomé Amar
Salomé AMAR
Stagiaire

Raphaël Delaygues
Raphaël DELAYGUES
Stagiaire

0467337903
Laura Henry
Laura HENRY
Stagiaire

Publications of the team

3-O sulfation of syndecan-1 mediated by the sulfotransferase HS3ST3a1 enhances myeloma aggressiveness.

Baert L, Manfroi B, Quintero M, Chavarria O, Barbon PV, Clement E, Zeller A, Van Kuppevelt T, Sturm N, Moreaux J, Tveita A, Bogen B, McKee T, Huard B

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Editorial: Transcriptional control in normal and malignant B-lymphocytes.

LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms.

Van Laethem F, Donaty L, Tchernonog E, Lacheretz-Szablewski V, Russello J, Buthiau D, Almeras M, Moreaux J, Bret C

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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

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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

Discovery of candidate DNA methylation cancer driver genes.

Pan H, Renaud L, Chaligne R, Bloehdorn J, Tausch E, Mertens D, Fink AM, Fischer K, Zhang C, Betel D, Gnirke A, Imielinski M, Moreaux J, Hallek M, Meissner A, Stilgenbauer S, Wu CJ, Elemento O, Landau DA

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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

RNA-sequencing data-driven dissection of human plasma cell differentiation reveals new potential transcription regulators.

Kassambara A, Herviou L, Ovejero S, Jourdan M, Thibaut C, Vikova V, Pasero P, Elemento O, Moreaux J

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Immunotherapy perspectives in the new era of B-cell editing.

Ueda N, Cahen M, Danger Y, Moreaux J, Sirac C, Cogné M

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma

Sara Ovejero, Jerome Moreaux

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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

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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

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[CD38 antibodies in multiple myeloma].

Moreaux J

CD38 antibodies in multiple myeloma

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Automated and Simplified Identification of Normal and Abnormal Plasma Cells in Multiple Myeloma by Flow Cytometry

Elina Alaterre, Sebastien Raimbault, Jean-Michel Garcia,Thierry Reme,Guilhem Requirand, Bernard Klein, and Jerome Moreaux

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Hypoxia favors the generation of human plasma cells

Michel Jourdan, Angélique Bruyer, Alboukadel Kassambara, Bernard Klein & Jérôme Moreaux

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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

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RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma

E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux

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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

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Identifying high-risk adult AML patients: epigenetic and genetic risk factors and their implications for therapy

Caroline Bret, Elena Viziteu, Alboukadel Kassambara & Jerome Moreaux

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Chetomin, targeting HIF-1a/p300 complex, exhibits antitumour activity in multiple myeloma

Elena Viziteu, Camille Grandmougin, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose, Bernard Klein, Jerome Moreaux

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DNA repair in diffuse large B-cell lymphoma: a molecular portrait

Caroline Bret, Bernard Klein, Guillaume Cartron, Jean-François Schved, Angelos Constantinou, Philippe Pasero, Jérôme Moreaux

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EZH2 in normal hematopoiesis and hematological malignancies

Laurie Herviou, Giacomo Cavalli, Guillaume Cartron, Bernard Klein and Jérôme Moreaux

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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

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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

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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

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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

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Gene expression-based risk score in diffuse large B-cell lymphoma

Caroline Bret, Bernard Klein, and Jérôme Moreaux

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Development of gene expression-based risk score in cytogenetically normal acute myeloid leukemia patients

Elias Bou Samra, Bernard Klein, Thérèse Commes, and Jérôme Moreaux

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Development of gene expression based score to predict sensitivity of multiple myeloma cells to DNA methylation

Jérôme Moreaux, Thierry Rème, Wim Leonard, et al.

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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

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A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines.

Moreaux J, Klein B, Bataille R, Descamps G, Maïga S, Hose D, Goldschmidt H, Jauch A, Rème T, Jourdan M, Amiot M, Pellat-Deceunynck C

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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

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Thèses et hdr

Genomic and epigenomic analyses for the development of precision medicine in multiple myeloma 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

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

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

DEVIN Julie
DEVIN Julie
Doctorant
BRUYER Angelique
BRUYER Angelique
ITA