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Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies.
Guièze, Romain; Liu, Vivian M; Rosebrock, Daniel; Jourdain, Alexis A; Hernández-Sánchez, María; Martinez Zurita, Aina; Sun, Jing; Ten Hacken, Elisa; Baranowski, Kaitlyn; Thompson, Philip A; Heo, Jin-Mi; Cartun, Zachary; Aygün, Ozan; Iorgulescu, J Bryan; Zhang, Wandi; Notarangelo, Giulia; Livitz, Dimitri; Li, Shuqiang; Davids, Matthew S; Biran, Anat; Fernandes, Stacey M; Brown, Jennifer R; Lako, Ana; Ciantra, Zoe B; Lawlor, Matthew A; Keskin, Derin B; Udeshi, Namrata D; Wierda, William G; Livak, Kenneth J; Letai, Anthony G; Neuberg, Donna; Harper, J Wade; Carr, Steven A; Piccioni, Federica; Ott, Christopher J; Leshchiner, Ignaty; Johannessen, Cory M; Doench, John; Mootha, Vamsi K; Getz, Gad; Wu, Catherine J.
Afiliação
  • Guièze R; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; CHU de Clermont-Ferrand, 63000 Clermont-Ferrand, Fr
  • Liu VM; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA.
  • Rosebrock D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jourdain AA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Hernández-Sánchez M; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer-IBMCC, Universidad de Salamanca, 37007 Salamanca, Spain; Servicio de Hemat
  • Martinez Zurita A; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sun J; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ten Hacken E; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA.
  • Baranowski K; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
  • Thompson PA; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
  • Heo JM; Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
  • Cartun Z; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
  • Aygün O; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Iorgulescu JB; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02215, USA.
  • Zhang W; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
  • Notarangelo G; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA.
  • Livitz D; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Li S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Davids MS; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
  • Biran A; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
  • Fernandes SM; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
  • Brown JR; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospita
  • Lako A; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Ciantra ZB; Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Lawlor MA; Harvard Medical School, Boston, MA 02215, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA.
  • Keskin DB; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA.
  • Udeshi ND; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Wierda WG; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
  • Livak KJ; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA.
  • Letai AG; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
  • Neuberg D; Harvard Medical School, Boston, MA 02215, USA; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Harper JW; Department of Cell Biology, Harvard Medical School, Boston, MA 02215, USA.
  • Carr SA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Piccioni F; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ott CJ; Harvard Medical School, Boston, MA 02215, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA.
  • Leshchiner I; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Johannessen CM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Doench J; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Mootha VK; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Getz G; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02214, USA.
  • Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Dana Building, Room DA-520, Boston MA 02215-02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospita
Cancer Cell ; 36(4): 369-384.e13, 2019 10 14.
Article em En | MEDLINE | ID: mdl-31543463
ABSTRACT
Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sulfonamidas / Leucemia Linfocítica Crônica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Compostos Bicíclicos Heterocíclicos com Pontes / Proteínas Proto-Oncogênicas c-bcl-2 / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: França
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sulfonamidas / Leucemia Linfocítica Crônica de Células B / Protocolos de Quimioterapia Combinada Antineoplásica / Compostos Bicíclicos Heterocíclicos com Pontes / Proteínas Proto-Oncogênicas c-bcl-2 / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Aged80 / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Cancer Cell Assunto da revista: NEOPLASIAS Ano de publicação: 2019 Tipo de documento: Article País de afiliação: França