ArticleOncogene2004
ERK couples chronic survival of NK cells to constitutively activated Ras in lymphoproliferative disease of granular lymphocytes (LDGL).
Article in Oncogene, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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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
42 citing papers in PubMed, 78 citations in OpenAlex.
- Trial
- Molecular Features and Diagnostic Challenges in Alpha/Beta T-Cell Large Granular Lymphocyte Leukemia.International journal of molecular sciences · 2022Article
- Cytokines in the Pathogenesis of Large Granular Lymphocytic Leukemia.Frontiers in oncology · 2022Review
- Large granular lymphocytic leukemia: a brief review.American journal of blood research · 2022Review
- Toward a Better Classification System for NK-LGL Disorders.Frontiers in oncology · 2022Review
- Large Granular Lymphocytic Leukemia: From Immunopathogenesis to Treatment of Refractory Disease.Cancers · 2021Review
- Article
- Aggressive NK Cell Leukemia: Current State of the Art.Cancers · 2020Review
- T-cell large granular lymphocyte leukemia in solid organ transplant recipients: case series and review of the literature.International journal of hematology · 2019Review
- Cell fate reprogramming by control of intracellular network dynamics.PLoS computational biology · 2015Article
- Suberoylanilide hydroxamic acid (SAHA) and cladribine synergistically induce apoptosis in NK-LGL leukaemia.British journal of haematology · 2015Article
- The pathogenesis and treatment of large granular lymphocyte leukemia.Blood reviews · 2014Review
- Fibrosis and subsequent cytopenias are associated with basic fibroblast growth factor-deficient pluripotent mesenchymal stromal cells in large granular lymphocyte leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Targeting IL-15 in large granular lymphocyte leukemia.Expert review of clinical immunology · 2013Article
- Some perspectives on network modeling in therapeutic target prediction.Biomedical engineering and computational biology · 2013Review
- Involvement of KRAS G12A mutation in the IL-2-independent growth of a human T-LGL leukemia cell line, PLT-2.Nagoya journal of medical science · 2012Article
- Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2.Hematology reports · 2012Article
- Large granular lymphocyte leukemia: from dysregulated pathways to therapeutic targets.Future oncology (London, England) · 2012Review
- Somatic STAT3 mutations in large granular lymphocytic leukemia.The New England journal of medicine · 2012Article
- Tipifarnib-mediated suppression of T-bet-dependent signaling pathways.Cancer immunology, immunotherapy : CII · 2012Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Chronic NK lymphoproliferative disease of large granular lymphocytes (LDGL) is characterized by the expansion of activated CD3-, CD16+ or CD56+ lymphocytes. The mechanism of survival of NK cells from LDGL patients is unknown but may be related to antigenic stimulation. There is currently no standard effective therapy for LDGL, and the disease is characteristically resistant to standard forms of chemotherapy. We found evidence of constitutive activation of extracellular-regulated kinase (ERK) in NK cells from 13/13 patients with NK-LDGL (one patient with aggressive and 12 patients with chronic disease). Ablation of ERK activity by inhibitors or a dominant-negative form of MEK, the upstream activator of ERK, reduced the survival of patient NK cells. Ras was also constitutively active in patient NK cells, and exposure of cells to the Ras inhibitor FTI2153 or to dominant-negative-Ras resulted not only in ERK inhibition but also in enhanced apoptosis in both the presence and absence of anti-Fas. Therefore, we conclude that a constitutively active Ras/MEK/ERK pathway contributes to the accumulation of NK cells in patients with NK-LDGL. These findings suggest that strategies to inhibit this signaling pathway may be useful for the treatment of the NK type of LDGL.
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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.