An Unbiased CRISPR-Cas9 Screening Method for the Identification of Positive and Negative Regulatory Proteins of Cell Adhesion.
Adhesion
B-cell receptor signaling
CRISPR-Cas9
Integrins
Kinases
Screening
Journal
Bio-protocol
ISSN: 2331-8325
Titre abrégé: Bio Protoc
Pays: United States
ID NLM: 101635102
Informations de publication
Date de publication:
05 Nov 2022
05 Nov 2022
Historique:
received:
30
06
2022
revised:
31
08
2022
accepted:
29
09
2022
entrez:
12
12
2022
pubmed:
13
12
2022
medline:
13
12
2022
Statut:
epublish
Résumé
Mature B-cell lymphomas are highly dependent upon the protective lymphoid organ microenvironment for their growth and survival. Targeting integrin-mediated homing and retention of the malignant B cells in the lymphoid organs, using the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, is a highly efficacious FDA-approved therapy for chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM). Unfortunately, a significant subset of patients is intrinsically resistant to ibrutinib or will develop resistance upon prolonged treatment. Here, we describe an unbiased functional genomic CRISPR-Cas9 screening method to identify novel proteins involved in B-cell receptor-controlled integrin-mediated adhesion, which provides novel therapeutic targets to overcome ibrutinib resistance. This screening method is highly flexible and can be easily adapted to identify cell adhesion-regulatory proteins and signaling pathways for other stimuli, adhesion molecules, and cell types. Graphical abstract.
Identifiants
pubmed: 36505024
doi: 10.21769/BioProtoc.4545
pii: e4545
pmc: PMC9711945
pii:
doi:
Types de publication
Journal Article
Langues
eng
Informations de copyright
Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.
Déclaration de conflit d'intérêts
Competing interests The authors have no competing interests to declare.
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