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Updated: Sep 8, 2025

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

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PARP1 Inhibition Halts EBV+ Lymphoma Progression by Disrupting the EBNA2/MYC Axis

Lisa Beatrice Caruso1, Giorgia Napoletani1, Samantha S Soldan1

  • 1The Wistar Institute, Philadelphia, Pennsylvania, USA.

Journal of Medical Virology
|July 7, 2025
PubMed

Insights

PARP1 inhibitors show potent antitumor effects against EBV-driven lymphoma by reprogramming gene expression. This approach targets the EBNA2/MYC pathway, offering a new treatment strategy for EBV-associated cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • Poly(ADP-ribose) polymerase 1 (PARP1) regulates Epstein-Barr virus (EBV) latency.
  • The therapeutic potential of PARP1 inhibitors in EBV-positive lymphomagenesis remains unexplored.

Purpose of the Study:

  • To investigate the therapeutic effect of PARP1 inhibitors on EBV-driven lymphomagenesis.
  • To elucidate the molecular mechanisms underlying the antitumor activity of PARP1 inhibition in EBV-associated cancers.

Main Methods:

  • Utilized a mouse xenograft model of EBV-driven lymphotytic cells (LCLs).
  • Assessed the effects of PARP1 inhibitor BMN 673 on LCLs in vivo and in vitro.
  • Analyzed transcriptional reprogramming, oncogene expression (MYC), viral oncoprotein (EBNA2), and chromatin association of key proteins (MYC, EBNA2, p53).

Main Results:

  • PARP1 inhibition with BMN 673 demonstrated significant antitumor effects against EBV-driven LCLs.
  • PARP1 inhibition led to substantial transcriptional reprogramming, primarily through the reduction of MYC oncogene expression and its targets.
  • Reduced expression of viral oncoprotein EBNA2 and blocked chromatin association of MYC, EBNA2, and p53.

Conclusions:

  • PARP1 plays a critical role in EBV-driven malignant transformation.
  • The EBNA2/MYC pathway is a key target of PARP1 inhibitors.
  • PARP1 inhibitors represent a promising therapeutic strategy for EBV-associated cancers driven by EBNA2.
Keywords:
BMN 673EBV‐associated cancerMYCPARP1lymphoma

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