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• W2911526677 abstract "Abstract 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." @default.
• W2911526677 created "2019-02-21" @default.
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• W2911526677 date "2019-01-24" @default.
• W2911526677 modified "2023-10-16" @default.
• W2911526677 title "BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo" @default.
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• W2911526677 doi "https://doi.org/10.1038/s41598-018-36853-8" @default.
• W2911526677 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6345919" @default.
• W2911526677 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30679590" @default.
• W2911526677 hasPublicationYear "2019" @default.
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