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

Abstract: Objectives
Paediatric Burkitt's lymphoma (pBL) is the most common childhood non-Hodgkin B-cell lymphoma. Despite the encouraging survival rates for most children, treating cases with relapse/resistance to current therapies remains challenging. CD38 is a transmembrane protein highly expressed in pBL. This study investigates the effectiveness of CD38-targeting monoclonal antibodies (mAbs), daratumumab and isatuximab, in impairing crucial cellular processes and survival pathways in pBL malignant cells.

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.

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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Clinical & Translational Immunology. - 13, 10 (2024) , e70011, ISSN: 2050-0068

Klassifikation und Themen

• Klassifikation: Medizin, Gesundheit

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2024
• Urheber: Kläsener, Anne Kathrin ; Herrmann, Nadja ; Håversen, Liliana ; Sundell, Timothy ; Sundqvist, Martina ; Lundqvist, Christina ; Manna, Paul T. ; Jonsson, Charlotte A. ; Visentini, Marcella ; Ljung Sass, Diana ; McGrath, Sarah ; Grimstad, Kristoffer ; Aranburu, Alaitz ; Mellgren, Karin ; Fogelstrand, Linda ; Forsman, Huamei ; Ekwall, Olov ; Borén, Jan ; Gjertsson, Inger ; Reth, Michael ; Mårtensson, Inga-Lill ; Camponeschi, Alessandro

Weitere Informationen

• DOI: 10.1002/cti2.70011
• URN: urn:nbn:de:bsz:25-freidok-2586697
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:23 MESZ