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Molecular classification and identification of an aggressive signature in low-grade B-cell lymphomas
Journal article   Open access   Peer reviewed

Molecular classification and identification of an aggressive signature in low-grade B-cell lymphomas

Melissa A Hopper, Kerstin Wenzl, Keenan T Hartert, Jordan E Krull, Abigail R Dropik, Joseph P Novak, Michelle K Manske, MaKayla R Serres, Vivekananda Sarangi, Melissa C Larson, …
Hematological oncology, Vol.41(4), pp.644-654
10/2023
DOI: 10.1002/hon.3187
PMCID: PMC10592585
PMID: 37254453
url
https://doi.org/10.1002/hon.3187View
Published (Version of record) Open Access

Abstract

Non-follicular low-grade B-cell lymphomas (LGBCL) are biologically diverse entities that share clinical and histologic features that make definitive pathologic categorization challenging. While most patients with LGBCL have an indolent course, some experience aggressive disease, highlighting additional heterogeneity across these subtypes. To investigate the potential for shared biology across subtypes, we performed RNA sequencing and applied machine learning approaches that identified five clusters of patients that grouped independently of subtype. One cluster was characterized by inferior outcome, upregulation of cell cycle genes, and increased tumor immune cell content. Integration of whole exome sequencing identified novel LGBCL mutations and enrichment of TNFAIP3 and BCL2 alterations in the poor survival cluster. Building on this, we further refined a transcriptomic signature associated with early clinical failure in two independent cohorts. Taken together, this study identifies unique clusters of LGBCL defined by novel gene expression signatures and immune profiles associated with outcome across diagnostic subtypes.
 Genetics transcriptomics immune signatures lymphoma

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