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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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Published in:HemaSphere 2023-08, Vol.7 (8), p.e931-n/a
Main Authors: 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
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cited_by cdi_FETCH-LOGICAL-c5748-bfbf8bee47f4bd97397e712e79cd742306fe0f6479ea5318c26d1489ab8e0e2a3
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creator 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
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.
doi_str_mv 10.1097/HS9.0000000000000931
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title The Nanomechanical Properties of CLL Cells Are Linked to the Actin Cytoskeleton and Are a Potential Target of BTK Inhibitors
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