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Sézary syndrome patient-derived models allow drug selection for personalized therapy

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dc.contributor.author Gallardo Hernández, Fernando
dc.contributor.author Andrades, Evelyn
dc.contributor.author Iglesias, Arnau
dc.contributor.author González, Jessica
dc.contributor.author Solé, Laura
dc.contributor.author Guillén, Yolanda
dc.contributor.author Blanco Ares, Gonzalo, 1989-
dc.contributor.author Colomo Saperas, Luis Alberto
dc.contributor.author Gimeno Vázquez, Eva
dc.contributor.author Conde Estévez, David
dc.contributor.author Rodríguez, Eva
dc.contributor.author Bielsa-Marsol, Isabel
dc.contributor.author Iglesias Coma, Mar
dc.contributor.author Bellosillo Paricio, Beatriz
dc.contributor.author Pujol Vallverdú, Ramon Maria
dc.contributor.author Regueiro, José R.
dc.contributor.author Bigas Salvans, Anna
dc.contributor.author Espinosa Blay, Lluís
dc.date.accessioned 2022-07-29T14:40:56Z
dc.date.available 2022-07-29T14:40:56Z
dc.date.issued 2022
dc.identifier.citation Gallardo F, Andrades E, Iglesias A, González J, Solé L, Guillén Y, Blanco G, Colomo L, Gimeno E, Conde D, Rodriguez E, Bielsa-Marso I, Iglesias M, Bellosillo B, Pujol RM, Regueiro JR, Bigas A, Espinosa L. Sézary syndrome patient-derived models allow drug selection for personalized therapy. Blood Adv. 2022 Jun 14;6(11):3410-21. DOI: 10.1182/bloodadvances.2021006860
dc.identifier.issn 2473-9529
dc.identifier.uri http://hdl.handle.net/10230/53891
dc.description.abstract Current therapeutic approaches for Sézary syndrome (SS) do not achieve a significant improvement in long-term survival of patients, and they are mainly focused on reducing blood tumor burden to improve quality of life. Eradication of SS is hindered by its genetic and molecular heterogeneity. Determining effective and personalized treatments for SS is urgently needed. The present work compiles the current methods for SS patient-derived xenograft (PDX) generation and management to provide new perspectives on treatment for patients with SS. Mononuclear cells were recovered by Ficoll gradient separation from fresh peripheral blood of patients with SS (N = 11). A selected panel of 26 compounds that are inhibitors of the main signaling pathways driving SS pathogenesis, including NF-kB, MAPK, histone deacetylase, mammalian target of rapamycin, or JAK/STAT, was used for in vitro drug sensitivity testing. SS cell viability was evaluated by using the CellTiter-Glo_3D Cell Viability Assay and flow cytometry analysis. We validated one positive hit using SS patient-derived Sézary cells xenotransplanted (PDX) into NOD-SCID-γ mice. In vitro data indicated that primary malignant SS cells all display different sensitivities against specific pathway inhibitors. In vivo validation using SS PDX mostly reproduced the responses to the histone deacetylase inhibitor panobinostat that were observed in vitro. Our investigations revealed the possibility of using high-throughput in vitro testing followed by PDX in vivo validation for selective targeting of SS tumor cells in a patient-specific manner.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher American Society of Hematology
dc.relation.ispartof Blood Adv. 2022 Jun 14;6(11):3410-21
dc.rights © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Sézary syndrome patient-derived models allow drug selection for personalized therapy
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1182/bloodadvances.2021006860
dc.subject.keyword Lymphoid neoplasia
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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