BRD4 inhibition sensitizes diffuse large B-cell lymphoma cells to ferroptosis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F23%3A10471842" target="_blank" >RIV/00216208:11110/23:10471842 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/23:10471842
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=mvIdpz7wv7" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=mvIdpz7wv7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/blood.2022019274" target="_blank" >10.1182/blood.2022019274</a>
Alternative languages
Result language
angličtina
Original language name
BRD4 inhibition sensitizes diffuse large B-cell lymphoma cells to ferroptosis
Original language description
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 patients with DLBCL, first-line multiagent 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. In this study, 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 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 expression and thus to 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood
ISSN
0006-4971
e-ISSN
1528-0020
Volume of the periodical
142
Issue of the periodical within the volume
13
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
1143-1155
UT code for WoS article
001098042200001
EID of the result in the Scopus database
2-s2.0-85166246687