B-cell receptor signaling activity identifies patients with mantle cell lymphoma at higher risk of progression.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 Mar 2024
19 Mar 2024
Historique:
received:
31
10
2023
accepted:
27
02
2024
medline:
20
3
2024
pubmed:
20
3
2024
entrez:
20
3
2024
Statut:
epublish
Résumé
Mantle cell lymphoma (MCL) is an incurable B-cell malignancy characterized by a high clinical variability. Therefore, there is a critical need to define parameters that identify high-risk patients for aggressive disease and therapy resistance. B-cell receptor (BCR) signaling is crucial for MCL initiation and progression and is a target for therapeutic intervention. We interrogated BCR signaling proteins (SYK, LCK, BTK, PLCγ2, p38, AKT, NF-κB p65, and STAT5) in 30 primary MCL samples using phospho-specific flow cytometry. Anti-IgM modulation induced heterogeneous BCR signaling responses among samples allowing the identification of two clusters with differential responses. The cluster with higher response was associated with shorter progression free survival (PFS) and overall survival (OS). Moreover, higher constitutive AKT activity was predictive of inferior response to the Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib. Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.
Identifiants
pubmed: 38503806
doi: 10.1038/s41598-024-55728-9
pii: 10.1038/s41598-024-55728-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6595Subventions
Organisme : Fondazione Italiana Linfomi (FIL)
ID : PGR Ed. 2019 to F.M.Q., MANTLE-FIRST BIO study, (https://clinicaltrials.gov/ct2/show/NCT04882475
Informations de copyright
© 2024. The Author(s).
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