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.
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.
a Department of Pathology , National University Cancer Institute of Singapore, National University Health System , Singapore.|b Yong Loo Lin School of Medicine.|c Cancer Science Institute of Singapore, National University of Singapore , Singapore.
Siok-Bian
SB
Ng
d Department of Pathology , Kurume University , Kurume , Japan.
Koichi
K
Ohshima
a Department of Pathology , National University Cancer Institute of Singapore, National University Health System , Singapore.
Viknesvaran
V
Selvarajan
c Cancer Science Institute of Singapore, National University of Singapore , Singapore.
Gaofeng
G
Huang
a Department of Pathology , National University Cancer Institute of Singapore, National University Health System , Singapore.
Shoa-Nian
SN
Choo
d Department of Pathology , Kurume University , Kurume , Japan.
Hiroaki
H
Miyoshi
e Department of Virology , Tokyo Medical and Dental University , Tokyo , Japan.
Norio
N
Shimizu
c Cancer Science Institute of Singapore, National University of Singapore , Singapore.
Renji
R
Reghunathan
f Department of Pediatrics , National University Health System , Singapore.
Hsin-Chieh
HC
Chua
f Department of Pediatrics , National University Health System , Singapore.
Allen Eng-Juh
AE
Yeoh
f Department of Pediatrics , National University Health System , Singapore.
Thuan-Chong
TC
Quah
g Department of Haematology-Oncology , National University Cancer Institute of Singapore, National University Health System , Singapore.
Liang-Piu
LP
Koh
f Department of Pediatrics , National University Health System , Singapore.
Poh-Lin
PL
Tan
b Yong Loo Lin School of Medicine.|c Cancer Science Institute of Singapore, National University of Singapore , Singapore.|g Department of Haematology-Oncology , National University Cancer Institute of Singapore, National University Health System , Singapore.
Wee-Joo
WJ
Chng
D000328:Adult; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002648:Child; D016000:Cluster Analysis; D000071221:Enhancer of Zeste Homolog 2 Protein; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D054391:Lymphoma, Extranodal NK-T-Cell / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2
EBV+ T/NK LPD in children; EZH2; cancer stem cell; molecular signature