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@ARTICLE{Schmitt:278355,
author = {A. Schmitt and M. Grimm and N. Kreienkamp and H. Junge and
J. Labisch and L. Schuhknecht and C. Schönfeld and E. S.
Görsch and A. Tibello and K. Menck and A. Bleckmann and C.
Lengerke and F. Rosenbauer and M. Grau and M. Zampieri and
K. Schulze Osthoff$^*$ and P. Klener and A. Dolnikova and G.
Lenz and S. Hailfinger},
title = {{BRD}4 inhibition sensitizes diffuse large {B}-cell
lymphoma cells to ferroptosis},
journal = {Blood},
volume = {12},
number = {10},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2023-01609},
pages = {e12363},
year = {2023},
note = {2023 Oct;12(10):e12363},
abstract = {Diffuse large B-cell lymphoma (DLBCL), the most common form
of non-Hodgkin lymphoma, is characterized by an aggressive
clinical course. In approximately one-third of DLBCL
patients, first-line multi-agent immunochemotherapy fails to
produce a durable response. Molecular heterogeneity and
apoptosis resistance pose major therapeutic challenges in
DLBCL treatment. To circumvent apoptosis resistance, the
induction of ferroptosis might represent a promising
strategy for lymphoma therapy. Here, a compound library
targeting epigenetic modulators was screened to identify
ferroptosis-sensitizing drugs. Strikingly, bromodomain and
extra-terminal domain (BET) inhibitors sensitized cells of
the germinal center B cell-like (GCB) subtype of DLBCL to
ferroptosis induction and the combination of BET inhibitors
with ferroptosis inducers, such as dimethyl fumarate (DMF)
or RSL3, synergized in the killing of DLBCL cells in vitro
and in vivo. On the molecular level, the BET protein BRD4
was found to be an essential regulator of ferroptosis
suppressor protein 1 (FSP1) expression and to thus protect
GCB-DLBCL cells from ferroptosis. Collectively, we
identified and characterized BRD4 as an important player in
ferroptosis suppression in GCB-DLBCL and provide a rationale
for the combination of BET inhibitors with
ferroptosis-inducing agents as a novel therapeutic approach
for DLBCL treatment.},
cin = {TU01},
ddc = {610},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37294920},
doi = {10.1182/blood.2022019274},
url = {https://inrepo02.dkfz.de/record/278355},
}