The clinical significance of c-MYC expression, rearrangement, and copy number gain in extranodal NK/T-cell lymphoma: A retrospective study in China

Chen, Yanping; Chen, Baozhen; Zhu, Weixing; Lin, Jian‐Li; Zhou, Yan; He, Tongmei; Lu, Jianping; Ye, Xing-an; Ma, Hu; Xu, C.; Chen, Gang

doi:10.1016/j.yexmp.2017.06.008

Cited by 3 publications

(3 citation statements)

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“…C-MYC is a well-known oncogene in lymphomas and is overexpressed in ENKTL, likely driven by LMP1 and EBV infection and causing upregulation of downstream targets EZH2 and RUNX3, the latter of which is a master transcriptional regulator and a putative oncogene in ENKTL [22,67,68]. C-MYC inhibitors are of particular interest in multiple aggressive lymphomas, and treatment of ENKTL cell lines with a small-molecule novel MYC inhibitor caused downregulation of both MYC and RUNX3 and, subsequently, apoptosis [67].…”

Section: C-mycmentioning

confidence: 99%

Rational Targets of Therapy in Extranodal NK/T-Cell Lymphoma

Major

Porcu

Haverkos

2023

Cancers

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Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) with poor outcomes, particularly in advanced-stage and relapsed/refractory disease. Emerging research on molecular drivers of ENKTL lymphomagenesis by next-generation and whole genome sequencing has revealed diverse genomic mutations in multiple signaling pathways, with the identification of multiple putative targets for novel therapeutic agents. In this review, we summarize the biological underpinnings of newly-understood therapeutic targets in ENKTL with a focus on translational implications, including epigenetic and histone regulatory aberrations, activation of cell proliferation signaling pathways, suppression of apoptosis and tumor suppressor genes, changes in the tumor microenvironment, and EBV-mediated oncogenesis. In addition, we highlight prognostic and predictive biomarkers which may enable a personalized medicine approach toward ENKTL therapy.

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Section: C-mycmentioning

confidence: 99%

Rational Targets of Therapy in Extranodal NK/T-Cell Lymphoma

Major

Porcu

Haverkos

2023

Cancers

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“…CD95 (Fas)/CD95 ligands (CD95L) are frequently expressed, and their expression is associated with the tissue damage and necrosis seen in ENKTL [29]. MYC is expressed in 50% of ENKTLs [30] and associated with a poor treatment response and prognosis. MYC gene rearrangement is not correlated with protein expression [30,31].…”

Section: Immunophenotypementioning

confidence: 99%

“…MYC is expressed in 50% of ENKTLs [30] and associated with a poor treatment response and prognosis. MYC gene rearrangement is not correlated with protein expression [30,31]. More than 30% of ENKTLs are positive for CD30, whose expression is significantly higher in the extranasal type than in the nasal type [32].…”

Section: Immunophenotypementioning

confidence: 99%

The Pathologic and Genetic Characteristics of Extranodal NK/T-Cell Lymphoma

Kim

2022

Life

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Extranodal NK/T-cell lymphoma is a neoplasm of NK cells or cytotoxic T cells presenting in extranodal sites, most often in the nasal cavity. The typical immunophenotypes are cCD3+, sCD3−, CD4−, CD5−, CD8−, CD16−, and CD56+ with the expression of cytotoxic molecules. Tumor subsets express NK cell receptors, CD95/CD95L, CD30, MYC, and PDL1. Virtually all the tumor cells harbor the EBV genome, which plays a key role in lymphomagenesis as an epigenetic driver. EBV-encoded oncoproteins modulate the host-cell epigenetic machinery, reprogramming the viral and host epigenomes using host epigenetic modifiers. NGS analysis revealed the mutational landscape of ENKTL, predominantly involving the JAK–STAT pathway, epigenetic modifications, the RNA helicase family, the RAS/MAP kinase pathway, and tumor suppressors, which indicate an important role of these pathways and this group of genes in the lymphomagenesis of ENKTL. Recently, three molecular subtypes were proposed, the tumor-suppressor/immune-modulator (TSIM), MGA-BRDT (MB), and HDAC9-EP300-ARID1A (HEA) subtypes, and they are well-correlated with the cell of origin, EBV pattern, genomic alterations, and clinical outcomes. A future investigation into the function and interaction of discovered genes would be very helpful for better understanding the molecular pathogenesis of ENKTL and establishing better treatment strategies.

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