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Diffuse large B-cell lymphoma with histone H3 trimethylation at lysine 27: another poor prognostic phenotype independent of c-Myc/Bcl2 coexpression

 Eun Ji Oh  ;  Woo Ick Yang  ;  June-Won Cheong  ;  Sung-eun Choi  ;  Sun Och Yoon 
 HUMAN PATHOLOGY, Vol.45(10) : 2043-2050, 2014 
Journal Title
Issue Date
Aged ; DNA Methylation/physiology* ; Enhancer of Zeste Homolog 2 Protein ; Female ; Histones/metabolism* ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse/genetics ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Lysine/metabolism ; Male ; Middle Aged ; Phenotype ; Polycomb Repressive Complex 2/biosynthesis ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins c-bcl-2/biosynthesis ; Proto-Oncogene Proteins c-myc/biosynthesis ; Tissue Array Analysis
Bcl2 ; Histone H3 trimethylation at lysine 27 ; Lymphoma, large B-cell, diffuse ; Prognosis ; c-Myc
Deregulation of histone H3 trimethylation at lysine 27 (H3K27me3) via aberration of the histone methyltransferase, enhancer of zeste homologue 2 (EZH2), is suggested to play a critical role in cancers including hematologic malignancies. In the present study, implications of H3K27me3 were investigated in diffuse large B-cell lymphoma (DLBCL) with respect to clinicopathological factors, especially in association with c-Myc/Bcl2 coexpression and germinal center B-like (GCB) or non-GCB subtype. By immunohistochemistry, a high level of H3K27me3 was observed in approximately one-third (35.3%, 79/224) of DLBCL cases, and this subset of cases was related to poor performance status (Eastern Cooperative Oncology Group scores ≥ 2) (P = .013), elevated lactate dehydrogenase level (P = .001), and a higher international prognostic index risk group (scores ≥3) (P = .005). H3K27me3 level was significantly correlated with EZH2 expression (P = .004) and c-Myc protein expression (P = .003) but not correlated with c-Myc/Bcl2 coexpression or with GCB or non-GCB subtype. A high level of H3K27me3 was related to an inferior overall survival (P = .006) and was shown to be an independent prognostic factor for overall survival along with the higher international prognostic index risk group and c-Myc/Bcl2 coexpression. In conclusion, H3K27me3 was related to EZH2 and c-Myc expression, suggesting formation of a MYC-EZH2-H3K27me3 loop in a subgroup of DLBCL cases. H3K27me3 was associated with poor patient outcome and revealed as an independent predictor for overall survival of DLBCL patients. H3K27me3 in DLBCL may be another high-risk phenotype independent of the phenotype of c-Myc/Bcl2 coexpression or other known poor prognostic subgroups.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
Choi, Sung Eun(최성은) ORCID logo https://orcid.org/0000-0002-6955-658X
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