EZH2 expression is dependent on MYC and TP53 regulation in diffuse large B-cell lymphoma
- PMID: 31991488
- DOI: 10.1111/apm.13029
EZH2 expression is dependent on MYC and TP53 regulation in diffuse large B-cell lymphoma
Abstract
EZH2 is an important epigenetic regulator, but its role in diffuse large B-cell lymphoma (DLBCL) pathogenesis and its relationship with MYC, BCL2, and TP53 expression, chromosomal rearrangements, and clinical features are still poorly understood. So, we investigated EZH2 expression and its associations with the immunophenotypic presentations, including MYC, BCL2, and TP53 expression, MYC, BCL2, and BCL6 translocation status, clinicopathological features, and therapeutic response to R-CHOP in a series of 139 DLBCL cases. EZH2 positivity was associated with MYC and TP53 expression (p = 0.0002 and p = 0.0000, respectively) and to high proliferative index (Ki67>70%, p = 0.0082). No associations were found among EZH2 expression and chromosomal translocation status. The non-germinal center (nGC) DLBCL presented most of associations observed in the general sample; however, only TP53 immunodetection showed associations with EZH2 expression in the germinal center (GC) DLBCL. EZH2 expression had no impact on therapeutic efficacy in R-CHOP-treated patients. In conclusion, EZH2 seems to be upregulated by MYC, to rely on TP53 alterations, and is associated with high proliferative tumors in DLBCL, which might be dependent on GC or nGC subclassifications. Furthermore, it is not a therapeutic efficacy marker to R-CHOP in our series.
Keywords: Diffuse large B-cell lymphoma; EZH2; MYC; R-CHOP; TP53.
© 2020 APMIS. Published by John Wiley & Sons Ltd.
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References
-
- Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med 2018;24:679-90.
-
- Karmali R, Gordon LI. Molecular subtyping in diffuse large B cell lymphoma: closer to an approach of precision therapy. Curr Treat Options Oncol 2017;18:11.
-
- Carbone A, Gloghini A, Kwong YL, Younes A. Diffuse large B cell lymphoma: using pathologic and molecular biomarkers to define subgroups for novel therapy. Ann Hematol 2014;93:1263-77.
-
- Boltežar L, Prevodnik VK, Perme MP, Gašljević G, Novaković B. Comparison of the algorithms classifying the ABC and GCB subtypes in diffuse large B-cell lymphoma. Oncol Lett 2018;15:6903-12.
-
- Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375-90.
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