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Updated: Jun 7, 2025
Multiplexed Fluorescent Immunohistochemical Staining, Imaging, and Analysis in Histological Samples of Lymphoma
Published on: January 9, 2019
Multilevel Analysis of MYC and BCL2 Aberrations in Diffuse Large B-Cell Lymphoma: Identifying a High-Risk Patient
Gayaththri Vimalathas1,2,3, Cecilie Steensboe Lang3, Tina Marie Green1,3
1Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Introduction:
Diffuse large B-cell lymphoma (DLBCL) exhibits striking clinical and biological heterogeneity. Recent studies have identified new subgroups within germinal center B-cell like (GCB) DLBCL, associated with inferior prognosis, irrespective of MYC and BCL2 translocations. We explored the existence of such a DLBCL high-risk subgroup, based on multilevel aberrations, especially focusing on MYC and BCL2.
Methods:
Tissue samples from 111 DLBCL patients were sequenced with a 90-gene lymphoma panel, followed by integrative analyses combining sequencing data, immunohistochemistry, fluorescent in situ hybridization, and clinical data.
Results:
We identified a high-risk subgroup in DLBCL defined by: dual immunohistochemical MYC and BCL2 expression (DEL), concurrent MYC and BCL2 translocations (DHL-BCL2), mutations in MYC, CXCR4, or both, and/or BCL2 amplification. The high-risk subgroup constituted 41% of the cohort and included DHL-BCL2, DEL, a GCB subgroup likely representing the recently described GCB subgroups, and a subset of non-GCB patients. In multivariate analysis, high-risk features provided independent predictive value from age and IPI. The 5-year overall survival was 36% in high-risk patients, compared to 76% in non-high-risk patients.
Conclusion:
We identified a distinct high-risk DLBCL subgroup, characterized by MYC and BCL2 aberrations, beyond conventional DHL-BCL2 and DEL, and irrespective of cell-of-origin, thereby expanding the poor-prognosis group.
