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

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.

Keywords::

• EBV+ T/NK LPD in children
• molecular signature
• cancer stem cell
• EZH2

Acknowledgements

S.-B.N. is supported by a National University Health System Clinician Scientist Program award. This work was partially supported by a grant from the Ministry of Education (MOE) Academic Research Fund (AcRF) Tier 1 (WBS No. R-179-000-046-112).

W.-J.C. is supported by a NMRC Clinician Scientist Investigator award. This work was partially supported by a Singapore Cancer Syndicate Grant, and the National Research Foundation Singapore and Singapore Ministry of Education under the Research Centers of Excellence initiative.

Potential conflict of interest

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Supplementary material available online

Supplementary Tables I–V and Figures 1–3 showing further data.