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Published on: January 9, 2018
The role of the polycomb repressive complex pathway in T and NK cell lymphoma: biological and prognostic implications
Soo Hee Kim1,2,3, Woo Ick Yang1, Yoo Hong Min4
1Department of Pathology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
Abstract:
Polycomb repressive complex 2 (PRC2; formed by EZH2, SUZ12, and EED protein subunits) and PRC1 (BMI1 protein) induce gene silencing through histone modification, primarily H3K27me3, and deregulation of PRC pathways leads to tumorigenesis. In the present study, activation of PRC2, H3K27me3, and BMI1 was investigated by immunohistochemistry in 175 cases of T and natural killer (NK) cell lymphoma. Activation of PRC proteins was analyzed according to c-MYC activation, Epstein-Barr virus (EBV) infection, CD30 activation, and survival. Among all T and NK cell lymphomas, high expression rates of 54.7 % for EZH2, 33.3 % for SUZ12, 85.7 % for EED, 40.5 % for H3K27me3, and 30.9 % for BMI1 were discovered. Activation of PRC2, H3K27me3, and BMI1 showed positive correlations (P < 0.05). Activation of c-MYC was associated with activation of SUZ12 and triple coactivation of all PRC2 protein subunits (EZH2(high)/SUZ12(high)/EED(high)) (P < 0.05). In EBV-positive tumors, activation of EZH2 and H3K27me3 showed greater association (P < 0.05). H3K27me3 and BMI1 showed a negative association in tumors expressing CD30 (P < 0.05). With respect to survival, BMI1 activation was independently associated with poor prognosis in T and NK cell lymphomas (P = 0.002). In conclusion, T and NK cell lymphomas were associated with activation of PRC pathway markers, for which c-MYC activation and EBV infection could be suggested as possible causes. PRC pathway markers may be potential therapeutic targets and prognostic markers in T and NK cell lymphoma.
Insights
Polycomb repressive complex (PRC) pathway markers are activated in T and natural killer (NK) cell lymphomas. BMI1 activation indicates a poor prognosis, suggesting PRC markers as potential therapeutic and prognostic targets.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Polycomb repressive complex 2 (PRC2) and PRC1 are key epigenetic regulators involved in gene silencing via histone modification (e.g., H3K27me3).
- Deregulation of PRC pathways is implicated in tumorigenesis, highlighting their importance in cancer development.
- Understanding PRC pathway activation in lymphoid malignancies is crucial for identifying potential therapeutic strategies.
Purpose of the Study:
- To investigate the activation status of PRC2 (EZH2, SUZ12, EED), H3K27me3, and BMI1 in T and natural killer (NK) cell lymphomas.
- To analyze the correlation between PRC pathway activation and c-MYC activation, Epstein-Barr virus (EBV) infection, CD30 expression, and patient survival.
- To evaluate the potential of PRC pathway markers as therapeutic targets and prognostic indicators in these lymphomas.
Main Methods:
- Immunohistochemistry was employed to assess the expression levels of EZH2, SUZ12, EED, H3K27me3, and BMI1 in 175 cases of T and NK cell lymphomas.
- Statistical analyses were performed to correlate PRC marker expression with clinical factors including c-MYC activation, EBV infection, CD30 status, and overall survival.
- Correlation and survival analyses, including assessment of independent prognostic value, were conducted.
Main Results:
- High expression rates were observed for EZH2 (54.7%), SUZ12 (33.3%), EED (85.7%), H3K27me3 (40.5%), and BMI1 (30.9%) in the studied lymphomas.
- Positive correlations were found between the activation of PRC2 components, H3K27me3, and BMI1 (P < 0.05).
- c-MYC activation correlated with SUZ12 and triple PRC2 coactivation. EBV positivity was associated with EZH2 and H3K27me3 activation. BMI1 activation was an independent predictor of poor prognosis (P = 0.002).
Conclusions:
- T and NK cell lymphomas exhibit activation of PRC pathway markers, potentially driven by c-MYC activation and EBV infection.
- BMI1 activation serves as a significant independent prognostic marker for poor survival in these lymphomas.
- PRC pathway markers represent promising therapeutic targets and prognostic tools for T and NK cell lymphomas.
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