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

Ng, Siok-Bian; Ohshima, Koichi; Selvarajan, V.; Huang, Gaofeng; Choo, Shoa-Nian; Miyoshi, Hiroaki; Shimizu, Norio; Reghunathan, Renji; Chua, Hsin-Chieh; Yeoh, Allen Eng Juh; Quah, Thuan-Chong; Koh, Liang-Piu; Tan, Poh Lin; Chng, Wee‐Joo

doi:10.3109/10428194.2014.983099

Cited by 9 publications

(10 citation statements)

References 30 publications

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“…Inhibition of JAK3 has been demonstrated to reduce the proliferation of ENKTL cells, indicating that targeting this pathway may be a potential therapeutic strategy (25). EZH2 has also been shown to be upregulated in EBV-TNKLPD-childhood and, similar to ENKTL, downregulation of EZH2 using a PRC2 inhibitor induces apoptosis in CAEBV cell lines (23, 26).…”

Section: Impact Of Transcriptomic Abnormalities On Understanding Disementioning

confidence: 99%

Transcriptomic Abnormalities in Epstein Barr Virus Associated T/NK Lymphoproliferative Disorders

et al. 2019

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Epstein Barr virus positive T/NK lymphoproliferative disorders (EBV-TNKLPD) comprise a spectrum of neoplasms ranging from cutaneous lymphoid proliferations to aggressive lymphomas. The spectrum includes extranodal NK/T-cell lymphoma (ENKTL), aggressive NK-cell leukemia, and a group of EBV-TNKLPDs affecting children which are poorly characterized in terms of their molecular biology. Gene and miRNA expression profiling has elucidated RNA abnormalities which impact on disease biology, classification, and treatment of EBV-TNKLPD. Pathways promoting proliferation, such as Janus associated kinase/ Signal Transducer and Activator of Transcription (JAK/STAT) and nuclear factor kB, are upregulated in ENKTL while upregulation of survivin and deregulation of p53 inhibit apoptosis in both ENKTL and chronic active EBV infection (CAEBV). Importantly, immune evasion via the programmed cell death-1 and its ligand, PD-1/PD-L1 checkpoint pathway, has been demonstrated to play an important role in ENKTL. Other pathogenic mechanisms involve EBV genes, microRNA deregulation, and a variety of other oncogenic signaling pathways. The identification of EBV-positive Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) as a tumor with a distinct molecular signature and clinical characteristics highlights the important contribution of the knowledge derived from gene and miRNA expression profiling in disease classification. Novel therapeutic targets identified through the study of RNA abnormalities provide hope for patients with EBV-TNKLPD, which often has a poor prognosis. Immune checkpoint inhibition and JAK inhibition in particular have shown promise and are being evaluated in clinical trials. In this review, we provide an overview of the key transcriptomic aberrancies in EBV-TNKLPD and discuss their translational potential.

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Section: Impact Of Transcriptomic Abnormalities On Understanding Disementioning

confidence: 99%

Transcriptomic Abnormalities in Epstein Barr Virus Associated T/NK Lymphoproliferative Disorders

et al. 2019

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“…For instance, among Hodgkin's lymphoma cells, there is a subset of clonal CD27 + /ALDH1A1 high cells that are thought to be the initiating cells for HL (21). In addition, ALDH1 expression is higher in Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoproliferative disorder in children and young adults (TNKLPDC) than in extranodal nasal NK/T-cell lymphoma, and it is correlated with the biological characteristics of stem cells (22). There is also a subset of clonogenic ALDH + cells in mantle cell lymphoma that are associated with multiple drug resistance (23).…”

Section: Discussionmentioning

confidence: 99%

The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma

et al. 2018

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Previously we showed that aldehyde dehydrogenase 1A1 (ALDH1A1) is a new mediator for resistance of DLBCL to CHOP and a facility predictor of clinical prognosis. In the present study, knockdown and inhibitor of ALDH1A1 were applied to identify the role of ALDH1A1 in Raji cells. CCK-8 and clone formation assay were applied to determine the CHOP sensitivity and clone formation ability. Caspase colorimetric assay and Annexin V/FITC staining was performed to determine the degree of apoptosis. Western blot analysis was used to detect the NF-κB/STAT3 signaling proteins and apoptotic-associated proteins. Real-time quantitative PCR (RT-PCR) was used to identify the differential expression of ALDH1A1 between NHL patients and healthy donors. We demonstrated that inhibition of ALDH1A1 increased the sensitivity of Raji cells to CHOP, as indicated by increased cytotoxicity, reduced clonogenicity, activated caspase-3/-9, decreased NF-κB/STAT3 signaling and increased pro-apoptosis signaling, ad increased apoptosis rate. Moreover, we found high ALDH1A1 expression was associated with poor prognosis in NHL patients. Our data revealed the critical role of ALDH1A1 in NHL and provides a theoretical basis for the use of ALDH1A1 inhibitors in NHL patients.

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“…SNT-8 is an EBV positive NKTCL cell line derived from primary lesions of a Japanese patient. SNK-10 and SNT-16 are EBV positive NKTCL cell lines derived from the peripheral blood of patients with chronic active EBV infection [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Resveratrol inhibits Extranodal NK/T cell lymphoma through activation of DNA damage response pathway

Sui

Zhou

Cao

et al. 2017

J Exp Clin Cancer Res

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Background: Extranodal NK/T cell lymphoma (NKTCL) is a highly aggressive non-Hodgkin lymphoma with poor prognosis. Resveratrol (RSV, 3,5,4′-trihydroxystilbene), a natural nontoxic phenolic compound found in the skin of grapes and some other spermatophytes, performs multiple bioactivities, such as antioxidant activity, anti-aging activity, reduction of cardiovascular disease risk and anticarcinogenic effect. Here we report the anti-tumor effect of RSV in NKTCL cell lines SNT-8, SNK-10 and SNT-16. Results: RSV inhibited NKTCL cell proliferation in a dose-and time-dependent manner and arrested cell cycle at S phase. It induced NKTCL cells apoptosis through mitochondrial pathway, shown as down-regulation of MCl-1 and survivin, up-regulation of Bax and Bad, and activation of caspase-9 and caspase-3. In addition, we found that RSV suppressed the phosphorylation level of AKT and Stat3, and activated DNA damage response (DDR) pathway directly or through up-regulation of Zta of Epstein-Barr virus (EBV). Furthermore, using KU55933 as the inhibitor of pATM, we verified that DDR played an important role in RSV inducing NKTCL apoptosis. RSV also showed synergistic effect on activating DDR pathway in combination with etoposide or ionizing radiation, which resulted in cell proliferation inhibition and apoptosis.

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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

Cited by 9 publications

References 30 publications

Transcriptomic Abnormalities in Epstein Barr Virus Associated T/NK Lymphoproliferative Disorders

Transcriptomic Abnormalities in Epstein Barr Virus Associated T/NK Lymphoproliferative Disorders

The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma

Resveratrol inhibits Extranodal NK/T cell lymphoma through activation of DNA damage response pathway

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