BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo.
Sci Rep
; 9(1): 701, 2019 01 24.
Article
em En
| MEDLINE
| ID: mdl-30679590
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Receptores de Antígenos de Linfócitos B
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Leucemia Linfocítica Crônica de Células B
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Proliferação de Células
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Proteína-Tirosina Quinase ZAP-70
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Fator de Transcrição STAT6
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Quinase Syk
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article