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Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies
dc.contributor.authorGuièze, Romain
dc.contributor.authorLiu, Vivian M.
dc.contributor.authorRosebrock, Daniel
dc.contributor.authorJourdain, Alexis A.
dc.contributor.authorSánchez Hernández, Ana María 
dc.contributor.authorMartinez Zurita, Aina
dc.contributor.authorSun, Jing
dc.contributor.authorTen Hacken, Elisa
dc.contributor.authorBaranowski, Kaitlyn
dc.contributor.authorThompson, Philip A.
dc.contributor.authorHeo, Jin-Mi
dc.contributor.authorCartun, Zachary
dc.contributor.authorAygün, Ozan
dc.contributor.authorIorgulescu, J. Bryan
dc.contributor.authorZhang, Wandi
dc.contributor.authorNotarangelo, Giulia
dc.contributor.authorLivitz, Dimitri
dc.contributor.authorLi, Shuqiang
dc.contributor.authorDavids, Matthew S.
dc.contributor.authorBiran, Anat
dc.contributor.authorFernandes, Stacey M.
dc.contributor.authorBrown, Jennifer R.
dc.contributor.authorLako, Ana
dc.contributor.authorCiantra, Zoe B.
dc.contributor.authorLawlor, Matthew A.
dc.contributor.authorKeskin, Derin B.
dc.contributor.authorUdeshi, Namrata D.
dc.contributor.authorWierda, William G.
dc.contributor.authorLivak, Kenneth J.
dc.contributor.authorLetai, Anthony G.
dc.contributor.authorNeuberg, Donna
dc.contributor.authorHarper, J. Wade
dc.contributor.authorCarr, Steven A.
dc.contributor.authorPiccioni, Federica
dc.contributor.authorOtt, Christopher J.
dc.contributor.authorLeshchiner, Ignaty
dc.contributor.authorJohannessen, Cory M.
dc.contributor.authorDoench, John
dc.contributor.authorMootha, Vamsi K.
dc.contributor.authorGetz, Gad
dc.contributor.authorWu, Catherine J.
dc.date.accessioned2021-05-24T09:41:12Z
dc.date.available2021-05-24T09:41:12Z
dc.date.issued2019
dc.identifier.citationGuièze, R., Liu, V. M., Rosebrock, D., Jourdain, A. A., Hernández-Sánchez, M., Martinez Zurita, A., Sun, J., Ten Hacken, E., Baranowski, K., Thompson, P. A., Heo, J. M., Cartun, Z., Aygün, O., Iorgulescu1, J. B., Zhang, W., Notarangelo, G., Livitz, D., Li, S., Davids, M. S., . . . Wu, C. J. (2019). Mitochondrial reprogramming underlies resistance to BCL-2 inhibition in lymphoid Malignancies. Cancer Cell, 36(4), 369–384. https://doi.org/10.1016/j.ccell.2019.08.005es_ES
dc.identifier.issn1535-6108
dc.identifier.urihttp://hdl.handle.net/10366/146272
dc.description.abstract[EN]Mitochondrial 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.es_ES
dc.language.isoenges_ES
dc.publisherCancer Celles_ES
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectBCL-2es_ES
dc.subjectVenetoclaxes_ES
dc.subjectChronic lymphocytic leukemiaes_ES
dc.subjectDrug resistancees_ES
dc.subjectGenome-wide screenes_ES
dc.subjectCRISPR/Cas9es_ES
dc.subjectClonal evolutiones_ES
dc.subjectMitochondriones_ES
dc.subjectMetabolismes_ES
dc.subjectAMPKes_ES
dc.subject.meshGenome*
dc.subject.meshLeukemia, Lymphocytic, Chronic, B-Cell*
dc.titleMitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancieses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publishversionhttps://doi.org/10.1016/j.ccell.2019.08.005
dc.subject.unesco3201.01 Oncologíaes_ES
dc.identifier.doi10.1016/j.ccell.2019.08.005
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.journal.titleCancer Celles_ES
dc.volume.number36es_ES
dc.issue.number4es_ES
dc.page.initial369es_ES
dc.page.final384.e13es_ES
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES
dc.subject.decsgenoma*
dc.subject.decsleucemia linfocítica crónica de células B*


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