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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2043-2050
Number of pages8
JournalHuman Pathology
Volume45
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

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Lymphoma, Large B-Cell, Diffuse
Histones
Lysine
Phenotype
Germinal Center
Survival
Proto-Oncogene Proteins c-myc
Hematologic Neoplasms
L-Lactate Dehydrogenase
Immunohistochemistry
Enhancer of Zeste Homolog 2 Protein
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

@article{151c6c2d4a3d434c9ab9317ae73d54bd,
title = "Diffuse large B-cell lymphoma with histone H3 trimethylation at lysine 27: Another poor prognostic phenotype independent of c-Myc/Bcl2 coexpression",
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.",
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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. / Oh, Eun Ji; Yang, Woo Ick; Cheong, June Won; Choi, Sung Eun; Yoon, Sun Och.

In: Human Pathology, Vol. 45, No. 10, 01.10.2014, p. 2043-2050.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Diffuse large B-cell lymphoma with histone H3 trimethylation at lysine 27

T2 - Another poor prognostic phenotype independent of c-Myc/Bcl2 coexpression

AU - Oh, Eun Ji

AU - Yang, Woo Ick

AU - Cheong, June Won

AU - Choi, Sung Eun

AU - Yoon, Sun Och

PY - 2014/10/1

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N2 - 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.

AB - 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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