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: 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
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/19304
Acceso en línea:http://hdl.handle.net/20.500.12105/19304
Access Level:acceso abierto
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spelling The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors.Sampietro, MartaCassina, ValeriaSalerno, DomenicoBarbaglio, FedericaBuglione, EnricoMarrano, Claudia AdrianaCampanile, RiccardoScarfò, LydiaBiedenweg, DoreenFregin, BobZamai, MorenoDíaz Torres, AlfonsaLabrador Cantarero, VeronicaGhia, PaoloOtto, OliverMantegazza, FrancescoCaiolfa, Valeria RScielzo, CristinaChronic 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 (LWW)German Centre for Cardiovascular ResearchUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Ministerio de Ciencia e Innovación (España)Fundación ProCNICMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)Unión Europea. Comisión Europea. 7 Programa Marco20242024-05-0820232023-08-0120232023-08-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/19304reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme FP7open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/193042026-06-12T12:43:37Z
dc.title.none.fl_str_mv 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.
spellingShingle The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors.
Sampietro, Marta
title_short 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_sort The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors.
dc.creator.none.fl_str_mv 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 Sampietro, Marta
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_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv German Centre for Cardiovascular Research
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Ministerio de Ciencia e Innovación (España)
Fundación ProCNIC
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
Unión Europea. Comisión Europea. 7 Programa Marco
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.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-08-01
2023
2023-08-01
2024
2024-05-08
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/19304
url http://hdl.handle.net/20.500.12105/19304
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme FP7
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams & Wilkins (LWW)
publisher.none.fl_str_mv Lippincott Williams & Wilkins (LWW)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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