Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance

Allison M Bock; Kerstin Wenzl; Joseph P Novak; Matthew E Stokes; Melissa A Hopper; Jordan E Krull; Abigail R Dropik; Vivek Sarangi; Maria Ortiz; Nicholas Stong; C Chris Huang; Matthew J Maurer; Rebecca L King; Umar Farooq; Yucai Wang; Thomas E Witzig; Stephen M Ansell; Thomas M Habermann; Grzegorz Nowakowski; James R Cerhan; Anne J Novak; Anita K Gandhi

doi:10.1002/hon.70006

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Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance

Journal article

Open access

Peer reviewed

Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance

Allison M Bock, Kerstin Wenzl, Joseph P Novak, Matthew E Stokes, Melissa A Hopper, Jordan E Krull, Abigail R Dropik, Vivek Sarangi, Maria Ortiz, Nicholas Stong, …

Hematological oncology, Vol.43(1), e70006

01/2025

DOI: 10.1002/hon.70006

PMCID: PMC11606593

PMID: 39612356

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https://doi.org/10.1002/hon.70006View

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Abstract

Diffuse large B-cell lymphoma (DLBCL) patients that fail to achieve a complete metabolic response with frontline immunochemotherapy have a poor prognosis. Genomic profiling has led to a broader understanding of the molecular drivers in DLBCL, but it is unknown how well current classifiers identify patients that will experience primary treatment resistance (PTR). Using whole exome and RNA sequencing data from newly diagnosed DLBCL patients, we evaluated the genomic landscape of PTR and compared it to that of non-PTR DLBCL. We found a significant increase in the frequency of TP53 (34% vs. 15%, p = 0.005) and ARID1A mutations (21% vs. 7%, p = 0.007) in PTR cases, with pathway analysis further demonstrating a downregulation of TP53 and an increase in chromatin modifying pathways. These results suggest that TP53 and ARID1A may be key mediators of PTR and important pathways contributing to the poor outcomes. We found that the current molecular classifiers were unable to identify PTR cases at diagnosis. However, our newly identified high-risk signature identified 46% of PTR cases at diagnosis. Overall, these results contribute to our understanding of the genomic landscape of patients with primary treatment resistance.

Mutation

Adult

Aged

Aged, 80 and over

Biomarkers, Tumor - genetics

DNA-Binding Proteins - genetics

Drug Resistance, Neoplasm - genetics

Female

Humans

Lymphoma, Large B-Cell, Diffuse - drug therapy

Lymphoma, Large B-Cell, Diffuse - genetics

Lymphoma, Large B-Cell, Diffuse - pathology

Male

Middle Aged

Prognosis

Transcription Factors - genetics

Tumor Suppressor Protein p53 - genetics

Details

Title: Subtitle: Molecular Features of Diffuse Large B-Cell Lymphoma Associated With Primary Treatment Resistance
Creators: Allison M Bock - Mayo Clinic
Kerstin Wenzl - Bristol-Myers Squibb
Joseph P Novak - Mayo Clinic
Matthew E Stokes - Bristol-Myers Squibb
Melissa A Hopper - Mayo Clinic
Jordan E Krull - Mayo Clinic
Abigail R Dropik - Mayo Clinic
Vivek Sarangi - Mayo Clinic in Florida
Maria Ortiz
Nicholas Stong - Bristol-Myers Squibb
C Chris Huang
Matthew J Maurer - Bristol-Myers Squibb
Rebecca L King - Mayo Clinic
Umar Farooq - University of Iowa
Yucai Wang - Mayo Clinic
Thomas E Witzig - Mayo Clinic
Stephen M Ansell - Mayo Clinic
Thomas M Habermann - Mayo Clinic
Grzegorz Nowakowski - Mayo Clinic
James R Cerhan - Bristol-Myers Squibb
Anne J Novak - Mayo Clinic
Anita K Gandhi - Bristol-Myers Squibb
Resource Type: Journal article
Publication Details: Hematological oncology, Vol.43(1), e70006
DOI: 10.1002/hon.70006
PMID: 39612356
PMCID: PMC11606593
NLM abbreviation: Hematol Oncol
ISSN: 1099-1069
eISSN: 1099-1069
Publisher: WILEY
Grant note: NIH HHS Tanoto Foundation Predolin Foundation Biobank
Language: English
Date published: 01/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
Record Identifier: 9984757065602771

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