An Unbiased CRISPR-Cas9 Screening Method for the Identification of Positive and Negative Regulatory Proteins of Cell Adhesion.

Autor:	Thus YJ; Department of Pathology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.; Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam, The Netherlands.; Cancer Biology and Immunology - Target & Therapy Discovery, Cancer Center Amsterdam (CCA), Amsterdam, The Netherlands., De Rooij MFM; Department of Pathology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.; Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam, The Netherlands.; Cancer Biology and Immunology - Target & Therapy Discovery, Cancer Center Amsterdam (CCA), Amsterdam, The Netherlands., Beijersbergen RL; Division of Molecular Carcinogenesis and Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands.; NKI Robotics and Screening Center and Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands., Spaargaren M; Department of Pathology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.; Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam, The Netherlands.; Cancer Biology and Immunology - Target & Therapy Discovery, Cancer Center Amsterdam (CCA), Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Bio-protocol [Bio Protoc] 2022 Nov 05; Vol. 12 (21). Date of Electronic Publication: 2022 Nov 05 (Print Publication: 2022).
DOI:	10.21769/BioProtoc.4545
Abstrakt:	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. Competing Interests: Competing interests The authors have no competing interests to declare. (Copyright © 2022 The Authors; exclusive licensee Bio-protocol LLC.)
Databáze:	MEDLINE
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