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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...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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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. |
format | Online Article Text |
id | pubmed-10365208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
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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