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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

Authors
 Eun Ji Oh  ;  Woo Ick Yang  ;  June-Won Cheong  ;  Sung-eun Choi  ;  Sun Och Yoon 
Citation
 Human Pathology, Vol.45(10) : 2043-2050, 2014 
Journal Title
 Human Pathology 
ISSN
 0046-8177 
Issue Date
2014
Abstract
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0046817714002846
DOI
10.1016/j.humpath.2014.07.002
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
Yonsei Authors
양우익(Yang, Woo Ick) ORCID logo https://orcid.org/0000-0002-6084-5019
윤선옥(Yoon, Sun Och) ORCID logo https://orcid.org/0000-0002-5115-1402
정준원(Cheong, June-Won) ORCID logo https://orcid.org/0000-0002-1744-0921
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100213
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