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Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies

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dc.contributor.authorGuièze, Romain
dc.contributor.authorLiu, Vivian M.
dc.contributor.authorRosebrock, Daniel
dc.contributor.authorJourdain, Alexis A.
dc.contributor.authorHernández Sánchez, María
dc.contributor.authorMartinez Zurita, Aina
dc.contributor.authorSun, Jing
dc.contributor.authorHacken, Elisa Ten
dc.contributor.authorLi, Shuqiang
dc.contributor.authorDavids, Matthew S.
dc.date.accessioned2024-11-28T10:32:05Z
dc.date.available2024-11-28T10:32:05Z
dc.date.issued2019-10
dc.description.abstractMitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDAapproved B-cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipSociedad Española de Hematología y Hemoterapia
dc.description.statuspub
dc.identifier.citationGuièze, Romain, et al. «Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies». Cancer Cell, vol. 36, n.o 4, octubre de 2019, pp. 369-384.e13. DOI.org (Crossref), https://doi.org/10.1016/j.ccell.2019.08.005.
dc.identifier.doi10.1016/j.ccell.2019.08.005
dc.identifier.issn1535-6108
dc.identifier.officialurlhttps://doi.org/10.1016/j.ccell.2019.08.005
dc.identifier.urihttps://hdl.handle.net/20.500.14352/111182
dc.issue.number4
dc.journal.titleCancer Cell
dc.language.isoeng
dc.page.final384
dc.page.initial369
dc.publisherCancer Cell
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.cdu577.1
dc.subject.cdu577.2
dc.subject.ucmBiología molecular (Farmacia)
dc.subject.ucmBioquímica (Farmacia)
dc.subject.unesco24 Ciencias de la Vida
dc.titleMitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies
dc.typejournal article
dc.type.hasVersionAM
dc.volume.number36
dspace.entity.typePublication
relation.isAuthorOfPublicationa4a145b6-73fb-465c-9c1b-969175cd85bd
relation.isAuthorOfPublication.latestForDiscoverya4a145b6-73fb-465c-9c1b-969175cd85bd

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