ArticleProceedings of the National Academy of Sciences of the United States of America2009
Lack of TNFalpha expression protects anaplastic lymphoma kinase-positive T-cell lymphoma (ALK+ TCL) cells from apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Different role of tumor necrosis factor-α polymorphism in non-Hodgkin lymphomas among Caucasian and Asian populations: a meta-analysis.International journal of molecular sciences · 2014Pooled it
- Updates in pathobiological aspects of anaplastic large cell lymphoma.Frontiers in oncology · 2023Review
- Review
- Article
- Crosstalk between microRNA and DNA Methylation Offers Potential Biomarkers and Targeted Therapies in ALK-Positive Lymphomas.Cancers · 2017Review
- Human splicing diversity and the extent of unannotated splice junctions across human RNA-seq samples on the Sequence Read Archive.Genome biology · 2016Article
- Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.Cell reports · 2016Article
- Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine in anaplastic large cell lymphoma.Biochimie · 2012Review
- Expression profiling after induction of demethylation in MCF-7 breast cancer cells identifies involvement of TNF-α mediated cancer pathways.Molecules and cells · 2012Article
- Oncogenic tyrosine kinase NPM-ALK induces expression of the growth-promoting receptor ICOS.Blood · 2011Article
- IL-2R common gamma-chain is epigenetically silenced by nucleophosphin-anaplastic lymphoma kinase (NPM-ALK) and acts as a tumor suppressor by targeting NPM-ALK.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- New developments in the pathology of malignant lymphoma: a review of the literature published from August to November 2009.Journal of hematopathology · 2009Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Here we report that T-cell lymphomas characterized by the expression of anaplastic lymphoma kinase (ALK+ TCL) fail to express the TNFalpha and frequently display DNA methylation of the TNFalpha gene promoter. While only a subset of the ALK+ TCL-derived cell lines showed a high degree of the promoter methylation, all 6 showed low to nondetectable expression of the TNFalpha mRNA, and none expressed the TNFalpha protein. All 14 ALK+ TCL tissue samples examined displayed some degree of the TNFalpha promoter methylation, which was the most prominent in the distal portion of the the promoter. Treatment with a DNA methyltransferase inhibitor, 5'-aza-2'-deoxy-cytidine (5-ADC), reversed the promoter methylation and led to the expression of TNFalpha mRNA and protein. Furthermore, in vitro DNA methylation of the promoter impaired its transcriptional activity in the luciferase reporter assay. This impairment was seen even if only either distal or proximal portion were methylated, with methylation of the former exerting a more profound inhibitory effect. Notably, the ALK+ TCL cell lines uniformly expressed the type 1 TNFalpha receptor (TNF-R1) protein known to transduce the TNFalpha-induced pro-apoptotic signals. Moreover, exogenous TNFalpha inhibited growth of the ALK+ TCL cell lines in a dose-dependent manner and induced activation of the members of the cell apoptotic pathway: Caspase 8 and caspase 3. These findings provide additional rationale for the therapeutic inhibition of DNA methyltransferases in ALK+ TCL. They also suggest that treatment with TNFalpha may be highly effective in this type of lymphoma.
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