Gene Expression Profiling Provides an Improved Characterization of CD79B-Mutated Diffuse Large B-Cell Lymphomas

Großmann L, Jagla W, Bettstetter M, Bertz S, Schwarz-Furlan S, Richter T, Dechow T, Decker T, Dreyling M, Sotlar K, Bartsch H, Hartmann A, Honecker J, Gaumann A (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 15

Article Number: 548

Journal Issue: 11

DOI: 10.3390/jpm15110548

Abstract

Background and Objectives: Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous neoplasms. CD79B and MYD88 mutations are associated with the activated B-cell-like (ABC) subtype of DLBCL and often co-occur and lead to constitutive activation of the NF-κB pathway. Several different genetic classifications to date have recognized CD79B- and MYD88-mutated DLBCLs as a unique subtype with poor response to therapy and unfavorable survival. However, little is known about gene expression in DLBCLs with mutated CD79B (and MYD88) in comparison to their wild type counterparts. The objective of this study was to compare the gene expression in DLBCLs according to their CD79B mutational status. Methods: A total of 48 primary, treatment-naïve DLBCLs (CD79B-mutated: 35%/n = 17, CD79B-wild type: 65%/n = 31) were investigated using RNA expression profiling (770 genes), followed by immunohistochemical analysis of the up-regulated genes and survival analysis. Results: The gene expression analysis revealed that downstream of CD79B CARD11 and the NF-κB targets NFKBIZ, IL10, IL12A, PIM1 and BCL2A1 were up-regulated in CD79B-mutated DLBCLs. The strongest up-regulation was detected for ARNT2 and WNT11. Other up-regulated genes included the apoptosis-related BID and granzyme B, as well as genes of cell cycle regulation such as RUNX1, RUNX1T1 and RASGRF1. Up-regulation was also found for IL7, STAT3, MLLT4, CD14 and the HSP90B1 subunit. TP53 mutation showed an association with poorer overall survival in a secondary analysis, consistent with prior reports, while survival by CD79B/MYD88 mutation status and the differentially expressed genes showed no significant differences in this cohort. Conclusions: In conclusion, the current study identified novel up-regulated genes in CD79B-mutated DLBCLs beyond NF-κB pathway signaling, which may contribute to a better definition of potential therapeutic targets and further improves the characterization of this distinct and aggressive DLBCL subgroup.

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Involved external institutions

Medizinisches Versorgungszentrum für Hämatologie und Onkologie Ravensburg Germany (DE) Institute für Pathologie Kaufbeuren-Ravensburg / Institute of Pathology Kaufbeuren-Ravensburg Germany (DE) Teilgemeinschaftspraxis Molekularpathologie Südbayern Germany (DE) Foundation Medicine GmbH Germany (DE) Ludwig-Maximilians-Universität (LMU) Germany (DE)

How to cite

APA:

Großmann, L., Jagla, W., Bettstetter, M., Bertz, S., Schwarz-Furlan, S., Richter, T.,... Gaumann, A. (2025). Gene Expression Profiling Provides an Improved Characterization of CD79B-Mutated Diffuse Large B-Cell Lymphomas. Journal of Personalized Medicine, 15(11). https://doi.org/10.3390/jpm15110548

MLA:

Großmann, Luis, et al. "Gene Expression Profiling Provides an Improved Characterization of CD79B-Mutated Diffuse Large B-Cell Lymphomas." Journal of Personalized Medicine 15.11 (2025).

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