1. Epstein–Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children and young adults has similar molecular signature to extranodal nasal natural killer/T-cell lymphoma but shows distinctive stem cell-like phenotype
- Author
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Allen Eng Juh Yeoh, Wee Joo Chng, Hiroaki Miyoshi, Hsin-Chieh Chua, Koichi Ohshima, Norio Shimizu, Poh Lin Tan, Viknesvaran Selvarajan, Quah Tc, Shoa-Nian Choo, Siok Bian Ng, Gaofeng Huang, L. P. Koh, and Renji Reghunathan
- Subjects
Adult ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Cancer Research ,Survivin ,Apoptosis ,Biology ,medicine.disease_cause ,Virus ,Inhibitor of Apoptosis Proteins ,Natural killer cell ,Young Adult ,Cancer stem cell ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Cluster Analysis ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Child ,Cell Proliferation ,Gene Expression Profiling ,Polycomb Repressive Complex 2 ,Hematology ,Natural killer T cell ,medicine.disease ,Epstein–Barr virus ,Lymphoproliferative Disorders ,Lymphoma ,Gene Expression Regulation, Neoplastic ,Lymphoma, Extranodal NK-T-Cell ,Gene expression profiling ,Phenotype ,medicine.anatomical_structure ,Oncology ,Immunology ,Neoplastic Stem Cells ,Tumor Suppressor Protein p53 ,Stem cell ,Transcriptome - Abstract
We performed gene expression profiling in Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoproliferative disorder in children and young adults (TNKLPDC) in order to understand the molecular pathways deregulated in this disease and compared it with nasal-type NK/T-cell lymphoma (NKTL). The molecular and phenotypic signature of TNKLPDC is similar to NKTL, with overexpression of p53, survivin and EZH2. Down-regulation of EZH2 in TNKLPDC cell lines led to an increase in apoptosis and decrease in tumor viability, suggesting that EZH2 may be important for the survival of TNKLPDC cells and hence potentially a useful therapeutic target. Notably, our gene expression profiling revealed a distinctive enrichment of stem cell related genes in TNKLPDC compared to NKTL. This was validated by a significantly higher expression of aldehyde dehydrogenase 1 (ALDH1) in TNKLPDC cell lines compared to NKTL cell lines. The novel discovery of cancer stem cell properties in TNKLPDC has potential therapeutic implications in this group of disorders.
- Published
- 2015
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