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.
Original language | English (US) |
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Article number | 101443 |
Journal | Cell Reports Medicine |
Volume | 5 |
Issue number | 3 |
DOIs | |
State | Published - Mar 19 2024 |
Keywords
- B cell
- follicular lymphoma
- genomics
- germinal center
- transcriptome
- tumor microenvironment
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology