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Updated: Jul 23, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Published on: January 22, 2019

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BET inhibitors induce NF-κB and E2F downregulation in Hodgkin and Reed-Sternberg cells

Sara Fernández1, Eva Díaz1, Claudia G Rita2

  • 1Translational Research Laboratory, MD Anderson Cancer Center Madrid, Spain.

Experimental Cell Research
|July 19, 2023
PubMed

Insights

Bromodomain and extra-terminal (BET) inhibitors show promise for treating classic Hodgkin lymphoma (cHL). These epigenetic therapies induce cell-cycle arrest and downregulate key pathways, supporting their use in select cHL patients.

Area of Science:

  • Oncology
  • Epigenetics
  • Hematology

Background:

  • Classic Hodgkin lymphoma (cHL) has a poor prognosis in relapsed/refractory settings, necessitating novel therapeutic strategies.
  • Epigenetic dysregulation is common in hematological malignancies, making epigenetic targets a rational approach.
  • Hodgkin and Reed-Sternberg (HRS) cells frequently exhibit mutations in CREBBP and EP300 acetyltransferases, suggesting sensitivity to bromodomain and extra-terminal (BET) inhibitors.

Purpose of the Study:

  • To confirm the efficacy of BET inhibitors (iBETs) in classic Hodgkin lymphoma (cHL) using cell models.
  • To explore the biological mechanisms underlying iBET treatment in cHL through whole-transcriptome analysis.

Main Methods:

  • Utilized representative cell models and functional experiments to assess iBET efficacy.
  • Conducted whole-transcriptome analyses to investigate molecular changes induced by iBETs.

Main Results:

  • BET inhibitors demonstrated cytostatic activity, inducing G1/S and G2/M cell-cycle arrest.
  • Observed variable downregulation of MYC.
  • Identified significant downregulation of critical pathways in cHL, including NF-kB and E2F, following iBET treatment.

Conclusions:

  • Findings support the therapeutic application of BET inhibitors (iBETs) in specific patient cohorts with classic Hodgkin lymphoma (cHL).
  • Revealed novel biological mechanisms and consequences of pan-BET inhibition in cHL.
Keywords:
BET inhibitorsClassic Hodgkin lymphomaE2FHodgkin and Reed–Sternberg cellsNF-κB

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