ArticleBlood2008
Molecular profiling of LGL leukemia reveals role of sphingolipid signaling in survival of cytotoxic lymphocytes.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 108 citations in OpenAlex.
- Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998).Leukemia · 2015Trial
- Transcriptomic landscape of CD8+ and CD4 + T-LGL leukemia revealed the distinct impact of STAT3 and STAT5B activating mutations.Leukemia · 2025Article
- Design and Synthesis of Novel PET Radiotracers for Imaging Sphingosine-1-Phosphate Receptor 5 (S1PR5) in the Brain.Journal of medicinal chemistry · 2025Article
- Identifying key genes and functionally enriched pathways in acute myeloid leukemia by weighted gene co-expression network analysis.Journal of applied genetics · 2025Article
- Pharmacological Effects of FTY720 and its Derivatives.Current topics in medicinal chemistry · 2024Review
- T-large granular lymphocytic leukemia.Blood research · 2023Review
- Molecular Features and Diagnostic Challenges in Alpha/Beta T-Cell Large Granular Lymphocyte Leukemia.International journal of molecular sciences · 2022Article
- Advancements on the Multifaceted Roles of Sphingolipids in Hematological Malignancies.International journal of molecular sciences · 2022Review
- Structural basis for receptor selectivity and inverse agonism in S1PNature communications · 2022Article
- Single-cell RNA sequencing coupled to TCR profiling of large granular lymphocyte leukemia T cells.Nature communications · 2022Article
- Pathogenesis and Treatment of T-Large Granular Lymphocytic Leukemia (T-LGLL) in the Setting of Rheumatic Disease.Frontiers in oncology · 2022Review
- 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
- Large Granular Lymphocytic Leukemia: From Immunopathogenesis to Treatment of Refractory Disease.Cancers · 2021Review
- Germline STAT3 gain-of-function mutations in primary immunodeficiency: Impact on the cellular and clinical phenotype.Biomedical journal · 2021Review
- Large granular lymphocyte leukemia serum and corresponding hematological parameters reveal unique cytokine and sphingolipid biomarkers and associations with STAT3 mutations.Cancer medicine · 2020Article
- Sphingosine kinase-2 is overexpressed in large granular lymphocyte leukaemia and promotes survival through Mcl-1.British journal of haematology · 2020Article
- Acid ceramidase promotes drug resistance in acute myeloid leukemia through NF-κB-dependent P-glycoprotein upregulation.Journal of lipid research · 2019Article
- Inclusion body myositis: clinical features and pathogenesis.Nature reviews. Rheumatology · 2019Review
- Chronic neutropenia in LGL leukemia and rheumatoid arthritis.Hematology. American Society of Hematology. Education Program · 2017Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
T-cell large granular lymphocyte (LGL) leukemia is characterized by clonal expansion of CD3(+)CD8(+) cells. Leukemic LGLs correspond to terminally differentiated effector-memory cytotoxic T lymphocytes (CTLs) that escape Fas-mediated activation-induced cell death (AICD) in vivo. The gene expression signature of peripheral blood mononuclear cells from 30 LGL leukemia patients showed profound dysregulation of expression of apoptotic genes and suggested uncoupling of activation and apoptotic pathways as a mechanism for failure of AICD in leukemic LGLs. Pathway-based microarray analysis indicated that balance of proapoptotic and antiapoptotic sphingolipid-mediated signaling was deregulated in leukemic LGLs. We further investigated sphingolipid pathways and found that acid ceramidase was constitutively overexpressed in leukemic LGLs and that its inhibition induced apoptosis of leukemic LGLs. We also showed that S1P(5) is the predominant S1P receptor in leukemic LGLs, whereas S1P(1) is down-regulated. FTY720, a functional antagonist of S1P-mediated signaling, induced apoptosis in leukemic LGLs and also sensitized leukemic LGLs to Fas-mediated death. Collectively, these results show a role for sphingolipid-mediated signaling as a mechanism for long-term survival of CTLs. Therapeutic targeting of this pathway, such as use of FTY720, may have efficacy in LGL leukemia.
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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.