Les plasmocytes sont des cellules effectrices critiques et les sentinelles à longue durée de vie de la mémoire immunitaire.
La maturation des cellules B doit être finement régulée pour assurer une réponse immunitaire efficace. Sur le plan transcriptionnel, la différenciation des cellules B en plasmocytes est associée à des remaniements coordonnés des profils d’expression géniques qui vont réprimer les gènes B et activer le programme d’expression plasmocytaire.
Ces modifications sont guidées par des facteurs de transcription B et plasmocytaires qui présentent des boucles de rétro-contrôle entre eux. Bien que le rôle complexe des facteurs de transcription impliqués dans la différenciation plasmocytaire ait été analysé, les mécanismes contrôlant ces remaniements transcriptionnels restent mal connus.
Nous recherchons à caractériser et comprendre les modifications épigénétiques, structurales, architecturales et le remodelage de la chromatine au cours de la différenciation plasmocytaire.
Nous nous attardons à identifier les voies impliquées dans ce remodelage de la chromatine et les impacts transcriptionnels sous-jacents. Nous recherchons aussi à comprendre les mécanismes oncogéniques au cours de la différenciation plasmocytaire pouvant conduire à l’émergence de néoplasies B matures.
Les hémopathies malignes des cellules B matures sont des cancers génétiquement et cliniquement hétérogènes. L'amélioration des traitements proviendra d'une meilleure caractérisation moléculaire pour développer des approches de médecine de précision prenant en compte l'hétérogénéité et l'évolution sous-clonale.
Notre laboratoire utilise les données de génomique, la bioinformatique et des modèles cellulaires uniques pour étudier les cellules B matures et les plasmocytes en nous focalisant sur les modifications épigénétiques et l'instabilité génomique. Ceci nous permet d’étudier la tumorigénèse, comprendre les mécanismes de progression et de résistance pour développer de nouveaux outils diagnostiques et thérapeutiques.
Ces travaux sont menés en lien avec d’autres équipes de l’IGH et les départements d’hématologie biologique et clinique du CHU de Montpellier.
A travers ces collaborations et nos implications au sein du laboratoire suivi des thérapies innovantes du CHU de Montpellier, dédié au diagnostic et suivi de la maladie résiduelle des patients atteints de néoplasies plasmocytaires, nous cherchons à accélérer le transfert des résultats issus de recherches fondamentales vers la clinique.
Nous avons également créé une société privée Diag2Tec pour valoriser les travaux de l’équipe.
Quantitative Integrative Survival Prediction in Multiple Myeloma Patients Treated With Bortezomib-Based Induction, High-Dose Therapy and Autologous Stem Cell Transplantation.
Hummel M, Hielscher T, Emde-Rajaratnam M, Salwender H, Beck S, Scheid C, Bertsch U, Goldschmidt H, Jauch A, Moreaux J, Seckinger A, Hose D
Brexucabtagene autoleucel in relapsed or refractory mantle cell lymphoma, intention-to-treat use in the DESCAR-T registry.
Herbaux C, Bret C, Bachy E, Bories P, Di Blasi R, Cuffel A, Gastinne T, Lamy T, Roussel M, Bouabdallah K, Beauvais D, Cartron G, Bay JO, Blaise D, Rubio MT, Mohty M, Le Bras F, Casasnovas O, Guy J, Guidez S, Llorente CC, Hermine O, La Rochelle LD, Carras S, Guffroy B, Caillat-Zucman S, Houot R, Le Gouill S
Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression in myelodysplastic neoplasms (MPO-MDS-Valid): protocol for a multicentre diagnostic accuracy study.
Planta C, Bret C, Manzoni D, Lhoumeau AC, Mayeur Rousse C, Ticchioni M, Campos L, Eischen A, Gonnet N, Merle R, Seigneurin A, Paul F, Comte E, Allieri-Rosenthal A, Tondeur S, Regnart C, Jacob MC, Labarère J, Park S, Raskovalova T
Integrative single-cell chromatin and transcriptome analysis of human plasma cell differentiation.
Alaterre E, Ovejero S, Bret C, Dutrieux L, Sika D, Fernandez Perez R, Espéli M, Fest T, Cogné M, Martín-Subero JI, Milpied P, Cavalli G, Moreaux J
Long-term results of Waldenström macroglobulinaemia treatment by bendamustine and rituximab: A study on behalf of the French Innovative Leukemia Organization (FILO).
Laribi K, Poulain S, Willems L, Merabet F, Herbaux C, Roos-Weil D, Laribi de Materre I, Roussel X, Nudel M, Tricot S, Dupuis J, Le Calloch R, Bareau B, Leblond V
An atlas of cells in the human tonsil.
Massoni-Badosa R, Aguilar-Fernández S, Nieto JC, Soler-Vila P, Elosua-Bayes M, Marchese D, Kulis M, Vilas-Zornoza A, Bühler MM, Rashmi S, Alsinet C, Caratù G, Moutinho C, Ruiz S, Lorden P, Lunazzi G, Colomer D, Frigola G, Blevins W, Romero-Rivero L, Jiménez-Martínez V, Vidal A, Mateos-Jaimez J, Maiques-Diaz A, Ovejero S, Moreaux J, Palomino S, Gomez-Cabrero D, Agirre X, Weniger MA, King HW, Garner LC, Marini F, Cervera-Paz FJ, Baptista PM, Vilaseca I, Rosales C, Ruiz-Gaspà S, Talks B, Sidhpura K, Pascual-Reguant A, Hauser AE, Haniffa M, Prosper F, Küppers R, Gut IG, Campo E, Martin-Subero JI, Heyn H
Combined inhibition of Wee1 and Chk1 as a therapeutic strategy in multiple myeloma.
Bruyer A, Dutrieux L, de Boussac H, Martin T, Chemlal D, Robert N, Requirand G, Cartron G, Vincent L, Herbaux C, Lutzmann M, Bret C, Pasero P, Moreaux J, Ovejero S
Immunophenotypic portrait of leukemia-associated-phenotype markers in B acute lymphoblastic leukemia.
Boris E, Theron A, Montagnon V, Rouquier N, Almeras M, Moreaux J, Bret C
RNA-sequencing based first choice of treatment and determination of risk in multiple myeloma.
Emde-Rajaratnam M, Beck S, Benes V, Salwender H, Bertsch U, Scheid C, Hänel M, Weisel K, Hielscher T, Raab MS, Goldschmidt H, Jauch A, Maes K, De Bruyne E, Menu E, De Veirman K, Moreaux J, Vanderkerken K, Seckinger A, Hose D
Extreme thrombocytosis with an aggressive evolution harboring a novel variant of calreticulin (CALR) in exon 3.
Bonnet S, Carillo S, Legrand B, Burroni B, Lavabre-Bertrand T, Requirand G, Robert N, Fornero L, Al Mansoori A, Moreaux J, Cartron G, Gabellier L, Herbaux C
Non-Relapse Mortality after CAR T-Cell therapy for Large B-Cell Lymphoma: A LYSA Study from the DESCAR-T Registry.
Lemoine J, Bachy E, Cartron G, Beauvais D, Gastinne T, Di Blasi R, Rubio MT, Guidez S, Mohty M, Casasnovas O, Joris M, Castilla-Llorente C, Haioun C, Hermine O, Loschi M, Carras S, Bories P, Fradon T, Herbaux C, Sesques P, Le Gouill S, Morschhauser F, Thieblemont C, Houot R
EZH2 targeting induces CD38 upregulation and response to anti-CD38 immunotherapies in multiple myeloma.
Chemlal D, Varlet E, Machura A, Ovejero S, Requirand G, Robert N, Cartron G, Alaterre E, Bret C, Vincent L, Herbaux C, Cavalli G, Bruyer A, De Boussac H, Moreaux J
Tandem versus single haematopoietic stem cell transplant and BV maintenance in relapsed/refractory Hodgkin lymphoma: A matched cohort analysis from the LYSA.
Marouf A, Molinari N, Sibon D, Cottereau AS, Kanoun S, Antoine C, Debureaux PE, Cavalieri D, Fornecker LM, Casasnovas RO, Herbaux C, Amorim S, Rossi C, Bouscary D, Brice P, Ghesquieres H, Tamburini J, Deau B
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
Prospective evaluation of lymphoma response to immunomodulatory therapy criteria in GATA trial from the LYSA group.
Al Tabaa Y, Casasnovas RO, Baillet C, Bachy E, Nicolas-Virelizier E, Schiano De Colella JM, Bailly C, Kanoun S, Guidez S, Gyan E, Gressin R, Morineau N, Ysebaert L, Le Gouill S, Tilly H, Houot R, Morschhauser F, Cartron G, Herbaux C
Randomized Phase III Trial Evaluating Subcutaneous Rituximab for the First-Line Treatment of Low-Tumor Burden Follicular Lymphoma: Results of a LYSA Study.
Cartron G, Bachy E, Tilly H, Daguindau N, Pica GM, Bijou F, Mounier C, Clavert A, Damaj GL, Slama B, Casasnovas O, Houot R, Bouabdallah K, Sibon D, Fitoussi O, Morineau N, Herbaux C, Gastinne T, Fornecker LM, Haioun C, Launay V, Araujo C, Benbrahim O, Sanhes L, Gressin R, Gonzalez H, Morschhauser F, Ternant D, Xerri L, Tarte K, Pranger D
Anti-PD-1 therapy can possibly reverse CAR T cells exhaustion in DLBCL.
Lamure S, Herbaux C
Editorial: Transcriptional control in normal and malignant B-lymphocytes.
Jerome Moreaux, Alexander A Shtil
Preventive plasmapheresis for rituximab related flare in cryoglobulinemic vasculitis.
Plain Language Summary of the iNNOVATE study: ibrutinib plus rituximab is well-tolerated and effective in people with Waldenström's macroglobulinemia.
Buske C, Tedeschi A, Trotman J, García-Sanz R, MacDonald D, Leblond V, Mahe B, Herbaux C, Matous JV, Tam CS, Heffner LT, Varettoni M, Palomba ML, Shustik C, Kastritis E, Treon SP, Ping J, Hauns B, Arango-Hisijara I, Dimopoulos MA
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
Salvage therapy with brentuximab-vedotin and bendamustine for patients with R/R PTCL: a retrospective study from the LYSA.
Damaj G, Aubrais R, Bouabdallah K, Chartier L, Herbaux C, Banos A, Brice P, Sibon D, Schiano JM, Cluzeau T, Laribi K, LE Calloch R, Bellal M, Delapierre B, Daguindau N, Amorim S, Agbetiafa K, Chauchet A, Besson C, Durot E, Bonnet C, Fouillet L, Bijou F, Tournilhac O, Gaulard P, Parrens MC
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
Ibrutinib as a treatment of hematologic autoimmune disorders in patients with indolent B-cell lymphoma.
Daniel A, Ghez D, Ravaiau C, Cavalieri D, Tournilhac O, Herbaux C, Roriz M, Wemeau M, Guillet S, Bossard JB, Hélène D, Kaphan E, Caroline R, Florence L, Pierache A, Michel M, Godeau B, Terriou L
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
Therapy-related Myeloid Neoplasms in Patients With Chronic Lymphocytic Leukemia Who Received FCR/FC as Frontline Therapy.
Laribi K, Baugier de Materre A, Ghez D, Dartigeas C, Tomowiak C, Mahé B, Micol JB, Merabet F, Leprêtre S, Herbaux C, Ysebaert L, Le Calloch R, Willems L, Voldoire M, Roos-Weil D, Bravetti C, Touileb Y, Davi F, Nguyen-Khac F, Maloum K, Béné MC
Can nivolumab alone cure patients with relapse or refractory Hodgkin lymphoma? A 5-year analysis of the French early access program (EPA).
Manson G, Herbaux C, Schiano JM, Casasnovas O, Stamatoullas A, Deau B, Schmitt A, Regny C, Bouabdallah K, Chauchet A, Ghesquieres H, Tempescul A, Dulery R, Nicolas-Virelizier E, Delmer A, Borel C, Dercle L, Brice P, Houot R, Lymphoma Study Association (LYSA)
The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias.
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
Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study.
Buske C, Tedeschi A, Trotman J, García-Sanz R, MacDonald D, Leblond V, Mahe B, Herbaux C, Matous JV, Tam CS, Heffner LT, Varettoni M, Palomba ML, Shustik C, Kastritis E, Treon SP, Ping J, Hauns B, Arango-Hisijara I, Dimopoulos MA
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
Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy.
Lamure S, Van Laethem F, De Verbizier D, Lozano C, Gehlkopf E, Tudesq JJ, Serrand C, Benzaoui M, Kanouni T, Quintard A, De Vos J, Tchernonog E, Platon L, Ayrignac X, Ceballos P, Sirvent A, François M, Guedon H, Quittet P, Mongellaz C, Conte A, Herbaux C, Bret C, Taylor N, Dardalhon V, Cartron G
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
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
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.
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
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
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
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
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
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
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
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
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