EBV-Associated Lymphoma Consortium Annual Meeting (Abstract)

Abstract Submission

Submission information

Submission Number: 9

Submission ID: 150860

Submission UUID: 9271ea5a-e361-47d8-9672-ef883fae9f73

Submission URI: /nci/ealv/venue/abstract

Submission Update: /nci/ealv/venue/abstract?token=obOmhOFguOW_2o_pLoW5rXK3I3yh2FgNIMmO3GsrSZA

Created: Wed, 09/03/2025 - 18:20

Completed: Wed, 09/03/2025 - 18:20

Changed: Wed, 09/03/2025 - 18:20

Remote IP address: 10.208.28.30

Submitted by: Anonymous

Language: English

Is draft: No

Webform: EBV-Associated Lymphoma Consortium Annual Meeting (Abstracts)

Submitted to: EBV-Associated Lymphoma Consortium Annual Meeting (Abstract)

OMB No.: 0925-0740
Expiration Date: 9/30/2025

Public reporting burden for this collection of information is estimated to average 60 minutes per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to: NIH, Project Clearance Branch, 6705 Rockledge Drive, MSC 7974, Bethesda, MD 20892-7974, ATTN: PRA (0925-0740). Do not return the completed form to this address.

Presenter Information

Please enter information for the person who will be the primary presenter/speaker/author.

First Name

Middle Initial

Last Name

Degree(s)

Please use the following formatting for these degrees: M.D. Ph.D. MPH

Position/Title/Career Status

Organization

Organization City/Town

Please provide a contact email for conference organizers to reach you.

Abstract Information

Abstract Keywords

Up to five keywords of your choice

Abstract Title

Abstract Summary

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma and the leading cause of cancer-related death in HIV-infected individuals. Up to 40% of individuals have refractory or relapsing DLBCL, and associated Epstein-Bar virus (EBV) coincides with even higher rates of mortality. Earlier, we showed that EBV activates Signal transducer and activator of transcription 3 (STAT3) leading to loss of the DNA damage response checkpoint and homologous recombination repair. While this ensures proliferation despite damage, it also increases reliance on alternate dsDNA break repair mechanisms. Targeting such parallel pathways represents a promising new approach to treatment known as synthetic lethality. Here, we investigate the gene expression profiles of EBV+-DLBCL tumors from HIV positive individuals to identify additional codependent DNA replication/repair pathways that may be targetable by synthetic lethal strategies. Five EBV+-DLBCL biopsies along with two matched normal tissue controls were obtained from the AIDS Cancer Specimen Resource. Immunohistochemistry confirmed the presence of CD20+ cells, EBV’s LMP-1, and proliferating cells marked by Ki67. Single nuclei suspensions were isolated from the frozen samples and subjected to barcoded cDNA amplification and sequencing using the PARSE single-nucleus RNA-seq protocol. Sequencing was performed on an Illumina NovaSeq to a depth of ~50,000–200,000 reads per nucleus. Only nuclei with >100 detected genes and < 15% mitochondrial gene content were retained for analysis. Data were processed by log-normalization and analyzed by shared near-neighbor and UMAP in Seurat. Analysis revealed varying cell types within and between the different samples as well as different degrees of malignant B cells. While ongoing, highly expressed genes enriched in malignant B cell populations varied greatly across samples. In addition to anticipated oncogenes, comparisons across samples and between the tumor tissues and matched normal control tissues reveal several genes involved in DNA replication, repair or metabolism.