Targeting CD38 with monoclonal antibodies disrupts key survival pathways in paediatric Burkitt's lymphoma malignant B cells

使用单克隆抗体靶向 CD38 会破坏儿童伯基特淋巴瘤恶性 B 细胞中的关键存活途径

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作者:Kathrin Kläsener, Nadja Herrmann, Liliana Håversen, Timothy Sundell, Martina Sundqvist, Christina Lundqvist, Paul T Manna, Charlotte A Jonsson, Marcella Visentini, Diana Ljung Sass, Sarah McGrath, Kristoffer Grimstad, Alaitz Aranburu, Karin Mellgren, Linda Fogelstrand, Huamei Forsman, Olov Ekwall, J

Conclusion

The study emphasises the therapeutic potential of CD38-targeting mAbs, particularly isatuximab, in pBL.

Methods

In silico analyses of patient samples, combined with in vitro experiments using the Ramos cell line, were conducted to assess the impact of daratumumab and isatuximab on cellular proliferation, apoptosis and the phosphoinositide 3-kinase (PI3K) pathway.

Results

Isatuximab was found to be more effective than daratumumab in disrupting B-cell receptor signalling, reducing cellular proliferation and inducing apoptosis. Additionally, isatuximab caused a significant impairment of the PI3K pathway and induced metabolic reprogramming in pBL cells. The study also revealed a correlation between CD38 and MYC expression levels in pBL patient samples, suggesting CD38 involvement in key oncogenic processes.

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