Follicular lymphoma B cells exhibit heterogeneous transcriptional states with associated somatic alterations and tumor microenvironments

Jordan E Krull; Kerstin Wenzl; Melissa A Hopper; Michelle K Manske; Vivekananda Sarangi; Matthew J Maurer; Melissa C Larson; Patrizia Mondello; ZhiZhang Yang; Joseph P Novak; Makayla Serres; Kaitlyn R Whitaker; Jose C Villasboas Bisneto; Thomas M Habermann; Thomas E Witzig; Brian K Link; Lisa M Rimsza; Rebecca L King; Stephen M Ansell; James R Cerhan; Anne J Novak

doi:10.1016/j.xcrm.2024.101443

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Follicular lymphoma B cells exhibit heterogeneous transcriptional states with associated somatic alterations and tumor microenvironments

Journal article

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Follicular lymphoma B cells exhibit heterogeneous transcriptional states with associated somatic alterations and tumor microenvironments

Jordan E Krull, Kerstin Wenzl, Melissa A Hopper, Michelle K Manske, Vivekananda Sarangi, Matthew J Maurer, Melissa C Larson, Patrizia Mondello, ZhiZhang Yang, Joseph P Novak, …

Cell reports. Medicine, Vol.5(3), 101443

03/2024

DOI: 10.1016/j.xcrm.2024.101443

PMCID: PMC10983045

PMID: 38428430

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Abstract

Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma of germinal center origin, which presents with significant biologic and clinical heterogeneity. Using RNA-seq on B cells sorted from 87 FL biopsies, combined with machine-learning approaches, we identify 3 transcriptional states that divide the biological ontology of FL B cells into inflamed, proliferative, and chromatin-modifying states, with relationship to prior GC B cell phenotypes. When integrated with whole-exome sequencing and immune profiling, we find that each state was associated with a combination of mutations in chromatin modifiers, copy-number alterations to TNFAIP3, and T follicular helper cells (Tfh) cell interactions, or primarily by a microenvironment rich in activated T cells. Altogether, these data define FL B cell transcriptional states across a large cohort of patients, contribute to our understanding of FL heterogeneity at the tumor cell level, and provide a foundation for guiding therapeutic intervention.

Genomics

B cell

follicular lymphoma

transcriptome

germinal center

tumor microenvironment

Details

Title: Subtitle: Follicular lymphoma B cells exhibit heterogeneous transcriptional states with associated somatic alterations and tumor microenvironments
Creators: Jordan E Krull - Mayo Clinic
Kerstin Wenzl - Mayo Clinic
Melissa A Hopper - Mayo Clinic
Michelle K Manske - Mayo Clinic
Vivekananda Sarangi - Mayo Clinic
Matthew J Maurer - Mayo Clinic
Melissa C Larson - Mayo Clinic
Patrizia Mondello - Mayo Clinic
ZhiZhang Yang - Mayo Clinic
Joseph P Novak - Mayo Clinic
Makayla Serres - Mayo Clinic
Kaitlyn R Whitaker - Mayo Clinic
Jose C Villasboas Bisneto - Mayo Clinic
Thomas M Habermann - Mayo Clinic
Thomas E Witzig - Mayo Clinic
Brian K Link - University of Iowa
Lisa M Rimsza - Mayo Clinic
Rebecca L King - Mayo Clinic
Stephen M Ansell - Mayo Clinic
James R Cerhan - Mayo Clinic
Anne J Novak - Mayo Clinic
Resource Type: Journal article
Publication Details: Cell reports. Medicine, Vol.5(3), 101443
DOI: 10.1016/j.xcrm.2024.101443
PMID: 38428430
PMCID: PMC10983045
NLM abbreviation: Cell Rep Med
eISSN: 2666-3791
Grant note: DOI: 10.13039/100000002, name: NIH; DOI: 10.13039/100002491, name: Bristol-Myers Squibb; DOI: 10.13039/100000054, name: National Cancer Institute, award: SPORE-P50 CA97274, R01 CA212162-01A1, U01 CA195568, 5T32AI007425-25
Language: English
Electronic publication date: 02/23/2024
Date published: 03/2024
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
Record Identifier: 9984562759802771

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