The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors.
Journal
HemaSphere
ISSN: 2572-9241
Titre abrégé: Hemasphere
Pays: United States
ID NLM: 101740619
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
29
12
2022
accepted:
15
06
2023
medline:
26
7
2023
pubmed:
26
7
2023
entrez:
26
7
2023
Statut:
epublish
Résumé
Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by an intense trafficking of the leukemic cells between the peripheral blood and lymphoid tissues. It is known that the ability of lymphocytes to recirculate strongly depends on their capability to rapidly rearrange their cytoskeleton and adapt to external cues; however, little is known about the differences occurring between CLL and healthy B cells during these processes. To investigate this point, we applied a single-cell optical (super resolution microscopy) and nanomechanical approaches (atomic force microscopy, real-time deformability cytometry) to both CLL and healthy B lymphocytes and compared their behavior. We demonstrated that CLL cells have a specific actomyosin complex organization and altered mechanical properties in comparison to their healthy counterpart. To evaluate the clinical relevance of our findings, we treated the cells in vitro with the Bruton's tyrosine kinase inhibitors and we found for the first time that the drug restores the CLL cells mechanical properties to a healthy phenotype and activates the actomyosin complex. We further validated these results in vivo on CLL cells isolated from patients undergoing ibrutinib treatment. Our results suggest that CLL cells' mechanical properties are linked to their actin cytoskeleton organization and might be involved in novel mechanisms of drug resistance, thus becoming a new potential therapeutic target aiming at the normalization of the mechanical fingerprints of the leukemic cells.
Identifiants
pubmed: 37492437
doi: 10.1097/HS9.0000000000000931
pmc: PMC10365208
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e931Informations de copyright
Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.
Déclaration de conflit d'intérêts
OO is the cofounder of Zellmechanik Dresden commercialising real-time deformability cytometry. PG is a HemaSphere editor. All the other authors have no conflicts of interest to disclose.
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