RT Journal Article
T1 Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies
A1 Guièze, Romain
A1 Liu, Vivian M.
A1 Rosebrock, Daniel
A1 Jourdain, Alexis A.
A1 Hernández Sánchez, María
A1 Martinez Zurita, Aina
A1 Sun, Jing
A1 Hacken, Elisa Ten
A1 Li, Shuqiang
A1 Davids, Matthew S.
AB 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 engineeredcell 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 combinatorialtherapy with metabolic modulators to address venetoclax resistance.
PB Cancer Cell
SN 1535-6108
YR 2019
FD 2019-10
LK https://hdl.handle.net/20.500.14352/111182
UL https://hdl.handle.net/20.500.14352/111182
LA eng
NO Guièze, 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.
NO Sociedad Española de Hematología y Hemoterapia
DS Docta Complutense
RD 13 may 2026