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The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors

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 cytos...

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Autores principales: Sampietro, Marta, Cassina, Valeria, Salerno, Domenico, Barbaglio, Federica, Buglione, Enrico, Marrano, Claudia Adriana, Campanile, Riccardo, Scarfò, Lydia, Biedenweg, Doreen, Fregin, Bob, Zamai, Moreno, Díaz Torres, Alfonsa, Labrador Cantarero, Veronica, Ghia, Paolo, Otto, Oliver, Mantegazza, Francesco, Caiolfa, Valeria R., Scielzo, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365208/
https://www.ncbi.nlm.nih.gov/pubmed/37492437
http://dx.doi.org/10.1097/HS9.0000000000000931
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author Sampietro, Marta
Cassina, Valeria
Salerno, Domenico
Barbaglio, Federica
Buglione, Enrico
Marrano, Claudia Adriana
Campanile, Riccardo
Scarfò, Lydia
Biedenweg, Doreen
Fregin, Bob
Zamai, Moreno
Díaz Torres, Alfonsa
Labrador Cantarero, Veronica
Ghia, Paolo
Otto, Oliver
Mantegazza, Francesco
Caiolfa, Valeria R.
Scielzo, Cristina
author_facet Sampietro, Marta
Cassina, Valeria
Salerno, Domenico
Barbaglio, Federica
Buglione, Enrico
Marrano, Claudia Adriana
Campanile, Riccardo
Scarfò, Lydia
Biedenweg, Doreen
Fregin, Bob
Zamai, Moreno
Díaz Torres, Alfonsa
Labrador Cantarero, Veronica
Ghia, Paolo
Otto, Oliver
Mantegazza, Francesco
Caiolfa, Valeria R.
Scielzo, Cristina
author_sort Sampietro, Marta
collection PubMed
description 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.
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spelling pubmed-103652082023-07-25 The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors Sampietro, Marta Cassina, Valeria Salerno, Domenico Barbaglio, Federica Buglione, Enrico Marrano, Claudia Adriana Campanile, Riccardo Scarfò, Lydia Biedenweg, Doreen Fregin, Bob Zamai, Moreno Díaz Torres, Alfonsa Labrador Cantarero, Veronica Ghia, Paolo Otto, Oliver Mantegazza, Francesco Caiolfa, Valeria R. Scielzo, Cristina Hemasphere Article 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. Lippincott Williams & Wilkins 2023-07-21 /pmc/articles/PMC10365208/ /pubmed/37492437 http://dx.doi.org/10.1097/HS9.0000000000000931 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Sampietro, Marta
Cassina, Valeria
Salerno, Domenico
Barbaglio, Federica
Buglione, Enrico
Marrano, Claudia Adriana
Campanile, Riccardo
Scarfò, Lydia
Biedenweg, Doreen
Fregin, Bob
Zamai, Moreno
Díaz Torres, Alfonsa
Labrador Cantarero, Veronica
Ghia, Paolo
Otto, Oliver
Mantegazza, Francesco
Caiolfa, Valeria R.
Scielzo, Cristina
The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
title The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
title_full The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
title_fullStr The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
title_full_unstemmed The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
title_short The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
title_sort nanomechanical properties of cll cells are linked to the actin cytoskeleton and are a potential target of btk inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365208/
https://www.ncbi.nlm.nih.gov/pubmed/37492437
http://dx.doi.org/10.1097/HS9.0000000000000931
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