BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo.
Fiche publication
Date publication
janvier 2019
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Pr FOURNEL Sylvie, Pr HERBRECHT Raoul, Pr MAUVIEUX Laurent, Dr VALLAT Laurent, Pr FORNECKER Luc-Matthieu, Pr MARTIN Thierry, Dr MIGUET Laurent
Tous les auteurs :
Schleiss C, Ilias W, Tahar O, Güler Y, Miguet L, Mayeur-Rousse C, Mauvieux L, Fornecker LM, Toussaint E, Herbrecht R, Bertrand F, Maumy-Bertrand M, Martin T, Fournel S, Georgel P, Bahram S, Vallat L
Lien Pubmed
Résumé
A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies.
Référence
Sci Rep. 2019 Jan 24;9(1):701