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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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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