ArticleProceedings of the National Academy of Sciences of the United States of America2011
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.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Uncovering a Novel Role of ROR1 in the Epigenetic Regulation of Tumor Suppressor Gene CREB3L1 in Triple-Negative Breast Cancer Cells.Biomolecules · 2025Article
- Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma.Leukemia · 2025Article
- Chimeric kinase ALK induces expression of NAMPT and selectively depends on this metabolic enzyme to sustain its own oncogenic function.Leukemia · 2023Article
- Mesenchymal stem cells, as glioma exosomal immunosuppressive signal multipliers, enhance MDSCs immunosuppressive activity through the miR-21/SP1/DNMT1 positive feedback loop.Journal of nanobiotechnology · 2023Article
- Updates in pathobiological aspects of anaplastic large cell lymphoma.Frontiers in oncology · 2023Review
- Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma.Frontiers in oncology · 2022Review
- Super-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma.Nature communications · 2021Article
- Synergistic Drug Combinations Prevent Resistance in ALK+ Anaplastic Large Cell Lymphoma.Cancers · 2021Article
- NPM-ALK-Induced Reprogramming of Mature TCR-Stimulated T Cells Results in Dedifferentiation and Malignant Transformation.Cancer research · 2021Article
- Requirement of DNMT1 to orchestrate epigenomic reprogramming for NPM-ALK-driven lymphomagenesis.Life science alliance · 2021Article
- Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma.Clinical epigenetics · 2020Review
- Systems and Synthetic microRNA Biology: From Biogenesis to Disease Pathogenesis.International journal of molecular sciences · 2019Review
- Review
- Disruption of STAT3-DNMT1 interaction by SH-I-14 induces re-expression of tumor suppressor genes and inhibits growth of triple-negative breast tumor.Oncotarget · 2017Article
- Crosstalk between microRNA and DNA Methylation Offers Potential Biomarkers and Targeted Therapies in ALK-Positive Lymphomas.Cancers · 2017Review
- NPM-ALK expression levels identify two distinct subtypes of paediatric anaplastic large cell lymphoma.Leukemia · 2017Article
- Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling.Cell reports · 2016Article
- Challenging perspectives on the cellular origins of lymphoma.Open biology · 2016Article
- STAT5 induces miR-21 expression in cutaneous T cell lymphoma.Oncotarget · 2016Article
- Anaplastic large cell lymphoma arises in thymocytes and requires transient TCR expression for thymic egress.Nature communications · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Anaplastic lymphoma kinase (ALK), physiologically expressed only by certain neural cells, becomes highly oncogenic, when aberrantly expressed in nonneural tissues as a fusion protein with nucleophosphin (NPM) and other partners. The reason why NPM-ALK succeeds in transforming specifically CD4(+) T lymphocytes remains unknown. The IL-2R common γ-chain (IL-2Rγ) is shared by receptors for several cytokines that play key roles in the maturation and growth of normal CD4(+) T lymphocytes and other immune cells. We show that IL-2Rγ expression is inhibited in T-cell lymphoma cells expressing NPM-ALK kinase as a result of DNA methylation of the IL-2Rγ gene promoter. IL-2Rγ promoter methylation is induced in malignant T cells by NPM-ALK. NPM-ALK acts through STAT3, a transcription factor that binds to the IL-2Rγ gene promoter and enhances binding of DNA methyltransferases (DNMTs) to the promoter. In addition, STAT3 suppresses expression of miR-21, which selectively inhibits DNMT1 mRNA expression. Reconstitution of IL-2Rγ expression leads to loss of the NPM-ALK protein and, consequently, apoptotic cell death of the lymphoma cells. These results demonstrate that the oncogenic tyrosine kinase NPM-ALK induces epigenetic silencing of the IL-2Rγ gene and that IL-2Rγ acts as a tumor suppressor by reciprocally inhibiting expression of NPM-ALK.
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