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

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

Content Provider	Scilit
Author	Guièze, Romain Liu, Vivian M. Rosebrock, Daniel Jourdain, Alexis A. Hernández-Sánchez, María Zurita, Aina Martinez Sun, Jing Hacken, Elisa Ten 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.
Copyright Year	2019
Description	Journal: Cancer Cell Summary 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.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801112/pdf http://www.cell.com/article/S1535610819303733/pdf
ISSN	15356108
e-ISSN	18783686
DOI	10.1016/j.ccell.2019.08.005
Journal	Cancer Cell
Issue Number	4
Volume Number	36
Language	English
Publisher	Elsevier BV
Publisher Date	2019-09-19
Access Restriction	Open
Subject Keyword	Journal: Cancer Cell Chronic Lymphocytic Leukemia Genome-wide Screen
Content Type	Text
Resource Type	Article
Subject	Cell Biology Cancer Research Oncology

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