Titre :

Continuous MYD88 Activation Is Associated With Expansion and Then Transformation of IgM Differentiating Plasma Cells

Auteur(s) :

Ouk, Catherine [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Roland, Lilian [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Gachard, Nathalie [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Poulain, Stéphanie [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Oblet, Christelle [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Rizzo, David [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Saintamand, Alexis [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Lemasson, Quentin [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Carrion, Claire [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Thomas, Morgane [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Balabanian, Karl [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Espéli, Marion [Auteur]
Ecotaxie, microenvironnement et développement lymphocytaire [EMily (UMR_S_1160 / U1160)]
Parrens, Marie [Auteur]
Service de pathologie [Bordeaux]
Soubeyran, Isabelle [Auteur]
Institut Bergonié [Bordeaux]
Boulin, Mélanie [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Faumont, Nathalie [Auteur]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Feuillard, Jean [Auteur correspondant]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]
Vincent-Fabert, Christelle [Auteur correspondant]
Contrôle de la Réponse Immune B et des Lymphoproliférations [CRIBL]

Titre de la revue :

Frontiers in immunology

Pagination :

641692

Éditeur :

Frontiers

Date de publication :

2021

ISSN :

1664-3224

Mot(s)-clé(s) en anglais :

MYD88 L265P mutation
lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia
IgM secretion
monoclonal Ig peak
B-cell lymphoma
plasma cell

Discipline(s) HAL :

Sciences du Vivant [q-bio]/Immunologie
Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hématologie
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]

Résumé en anglais : [en]

Activating mutations of MYD88 ( MYD88 L265P being the far most frequent) are found in most cases of Waldenström macroglobulinemia (WM) as well as in various aggressive B-cell lymphoma entities with features of plasma cell ...
Lire la suite >Activating mutations of MYD88 ( MYD88 L265P being the far most frequent) are found in most cases of Waldenström macroglobulinemia (WM) as well as in various aggressive B-cell lymphoma entities with features of plasma cell (PC) differentiation, such as activated B-cell type diffuse large B-cell lymphoma (DLBCL). To understand how MYD88 activation exerts its transformation potential, we developed a new mouse model in which the MYD88 L252P protein, the murine ortholog of human MYD88 L265P , is continuously expressed in CD19 positive B-cells together with the Yellow Fluorescent Protein (Myd88 L252P mice). In bone marrow, IgM B and plasma cells were expanded with a CD138 expression continuum from IgM high CD138 low to IgM low CD138 high cells and the progressive loss of the B220 marker. Serum protein electrophoresis (SPE) longitudinal analysis of 40 Myd88 L252P mice (16 to 56 weeks old) demonstrated that ageing was first associated with serum polyclonal hyper gammaglobulinemia (hyper Ig) and followed by a monoclonal immunoglobulin (Ig) peak related to a progressive increase in IgM serum levels. All Myd88 L252P mice exhibited spleen enlargement which was directly correlated with the SPE profile and was maximal for monoclonal Ig peaks. Myd88 L252P mice exhibited very early increased IgM PC differentiation. Most likely due to an early increase in the Ki67 proliferation index, IgM lymphoplasmacytic (LP) and plasma cells continuously expanded with age being first associated with hyper Ig and then with monoclonal Ig peak. This peak was consistently associated with a spleen LP-like B-cell lymphoma. Clonal expression of both membrane and secreted µ chain isoforms was demonstrated at the mRNA level by high throughput sequencing. The Myd88 L252P tumor transcriptomic signature identified both proliferation and canonical NF-κB p65/RelA activation. Comparison with MYD88 L265P WM showed that Myd88 L252P tumors also shared the typical lymphoplasmacytic transcriptomic signature of WM bone marrow purified tumor B-cells. Altogether these results demonstrate for the first time that continuous MYD88 activation is specifically associated with clonal transformation of differentiating IgM B-cells. Since MYD88 L252P targets the IgM PC differentiation continuum, it provides an interesting preclinical model for development of new therapeutic approaches to both WM and aggressive MYD88 associated DLBCLs.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Projet ANR :

Analyse integrative de la biologie des plasmocytes normaux et pathologiques
Impact des SNARE sur la biologie des plasmocytes
Autocrinie et paracrinie de l'axe de signalisation CXCL12/CXCR4-CXCR7 dans la niche ostéo-vasculaire: impact sur la spécification et l'engagement lymphoïde des cellules souches hématopoïétiques

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Date de dépôt :

2024-02-17T04:15:50Z