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 language | English |
|---|---|
| Pages (from-to) | 2043-2050 |
| Number of pages | 8 |
| Journal | Human Pathology |
| Volume | 45 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2014 Oct 1 |
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All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine
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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 journal › Article
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
Y1 - 2014/10/1
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.
UR - http://www.scopus.com/inward/record.url?scp=84908208783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908208783&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2014.07.002
DO - 10.1016/j.humpath.2014.07.002
M3 - Article
C2 - 25149548
AN - SCOPUS:84908208783
VL - 45
SP - 2043
EP - 2050
JO - Human Pathology
JF - Human Pathology
SN - 0046-8177
IS - 10
ER -