ArticleBlood cancer discovery2022
Identification and Targeting of the Developmental Blockade in Extranodal Natural Killer/T-cell Lymphoma.
Article in Blood cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Azacitidine-induced remission enables allogeneic transplantation inHaematologica · 2026Article
- Article
- DNA methylation-based classification of hematolymphoid neoplasms.Blood advances · 2026Article
- Viral-driven oncogenesis in T/NK-cell lymphomas: parallels and divergences between HTLV-1 and EBV.International journal of hematology · 2026Review
- Gene Regulatory Programs of NK Cells Show That NCAM1 (CD56) and KIRs Are Controlled by Genetically Polymorphic Distal Regulatory Elements.European journal of immunology · 2026Article
- Molecular pathogenesis and evolving treatment landscape of extranodal NK/T-cell lymphoma.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2026Review
- Epstein-Barr Virus-Associated T/NK-Cell Neoplasms.Journal of medical virology · 2026Review
- Priming with DNMT Inhibitors Potentiates PD-1 Immunotherapy by Triggering Viral Mimicry in Relapsed/Refractory NK/T-cell Lymphoma.Cancer discovery · 2025Article
- Single-cell and spatial transcriptomics reveal intratumor heterogeneity and immune evasion in natural killer/T cell lymphoma.iScience · 2025Article
- Extranodal NK/T-cell lymphoma: an update of the molecular characterization of the tumor and microenvironment, and its clinical implications.The Lancet regional health. Western Pacific · 2025Review
- The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.Clinical and experimental medicine · 2025Review
- Diagnostic challenge presented by extranodal NK/T cell lymphoma expressing CD20, CD30 and CD15: A case report.Oncology letters · 2025Article
- Expression of senescence-related CD161 promotes extranodal NK/T cell lymphoma by affecting T cell phenotype and cell cycle.Molecular medicine (Cambridge, Mass.) · 2024Article
- Modeling NK-cell lymphoma in mice reveals its cell-of-origin and microenvironmental changes and identifies therapeutic targets.Nature communications · 2024Article
- Single-Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T-Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.iScience · 2023Article
- Effects of epigenetic therapy on natural killer cell function and development in hematologic malignancy.Journal of leukocyte biology · 2023Review
- Review
- Article
- Treatment of extranodal NK/T-cell lymphoma: From past to future.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
39 authors at 14 institutions in 5 countries.
Funding
Abstract
Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive, rare lymphoma of natural killer (NK) cell origin with poor clinical outcomes. Here we used phenotypic and molecular profiling, including epigenetic analyses, to investigate how ENKTL ontogeny relates to normal NK-cell development. We demonstrate that neoplastic NK cells are stably, but reversibly, arrested at earlier stages of NK-cell maturation. Genes downregulated in the most epigenetic immature tumors were associated with polycomb silencing along with genomic gain and overexpression of EZH2. ENKTL cells exhibited genome-wide DNA hypermethylation. Tumor-specific DNA methylation gains were associated with polycomb-marked regions, involving extensive gene silencing and loss of transcription factor binding. To investigate therapeutic targeting, we treated novel patient-derived xenograft (PDX) models of ENKTL with the DNA hypomethylating agent, 5-azacytidine. Treatment led to reexpression of NK-cell developmental genes, phenotypic NK-cell differentiation, and prolongation of survival. These studies lay the foundation for epigenetic-directed therapy in ENKTL. SIGNIFICANCE: Through epigenetic and transcriptomic analyses of ENKTL, a rare, aggressive malignancy, along with normal NK-cell developmental intermediates, we identified that extreme DNA hypermethylation targets genes required for NK-cell development. Disrupting this epigenetic blockade in novel PDX models led to ENKTL differentiation and improved survival. This article is highlighted in the In This Issue feature, p. 85.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.