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Prognostic Analyses of Genetic Subtypes Within Diffuse Large B-Cell Lymphoma

By: Gavin Calabretta, BS
Posted: Wednesday, April 6, 2022

Seeking to evaluate the prognostic roles of the MYC and BCL2 oncogenes, genetic features, as well as different microenvironment biomarkers in aggressive B-cell lymphoma, Ken H. Young, MD, PhD, of Duke University Medical Center, and colleagues retrospectively analyzed a large cohort of diffuse large B-cell lymphoma (DLBCL) subtypes. The study, which was published in Clinical Cancer Research, evaluated MYC/BCL2 expression, genetic mutations, immune cell counts, and immune checkpoint expression, with the objective of testing genetic subtyping as a potential way to stratify patients with double-expressor DLBCL and vice versa (phenotyping to stratify DLBCL genetic subtypes).   

“We performed correlative and prognostic analyses within and across DLBCL genetic subtypes and MYC/BCL2 double-expressors,” stated the study authors. “Together, these results demonstrated independent and additive prognostic effects of phenotypic MYC/BCL2/microenvironment biomarkers and genetic subtyping in DLBCL prognostication.”

As part of the DLBCL Consortium Study Program, the study authors analyzed 424 adult cases of de novo DLBCL, for which targeted next-generation sequencing was performed. Both conventional and fluorescent multiplex immunohistochemistry were used, along with a gene-expression signature analysis. Cells were classified based on phenotypic marker expression, and phenotype-positive cell counts were quantified for each marker. The LymphGen classification tool was implemented to classify genetic subtypes from obtained sequencing data.

The authors observed distinct gene-expression signatures among genetic subtypes, and MYC/BCL2 double-high-expression (DhE) by immunohistochemistry had a significant adverse effect on prognosis within the EZB genetic subtype and LymphGen-unclassified cases, but this was not the case for the MCD and ST2 subtype. In contrast, DhE—but not non-DhE—was stratified by KMT2D mutations. Although prognostically favorable in BN2, MCD, and DhE, high T-cell infiltration levels showed an antagonistic effect in ST2 and LymphGen-unclassified cases. High FN1 and PD-1 expression yielded detrimental effects in multiple subgroups. Lastly, the authors reported that the prognostic effects of DhE and immune biomarkers were independent, although high Ki67 expression and DhE were associated with lower T-cell infiltration in LymphGen-unclassified cases.

Disclosure: For full disclosures of the study authors, visit

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