ArticleBlood2006
Phosphatidylinositol-3-phosphate kinase pathway activation protects leukemic large granular lymphocytes from undergoing homeostatic apoptosis.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 81 citations in OpenAlex.
- Trial
- Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998).Leukemia · 2015Trial
- KLRG1 re-defines a leukemic clone of CD8 effector T cells sensitive to PI3K inhibitor in T cell large granular lymphocytic leukemia.Cell reports. Medicine · 2025Article
- Molecular Features and Diagnostic Challenges in Alpha/Beta T-Cell Large Granular Lymphocyte Leukemia.International journal of molecular sciences · 2022Article
- Article
- 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
- Article
- Ruxolitinib with resminostat exert synergistic antitumor effects in Cutaneous T-cell Lymphoma.PloS one · 2021Article
- Divergent roles for antigenic drive in the aetiology of primary versus dasatinib-associated CD8Scientific reports · 2018Article
- PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia.Oncotarget · 2015Article
- Cell fate reprogramming by control of intracellular network dynamics.PLoS computational biology · 2015Article
- Mantle cell lymphoma concurrent with T-large granular lymphocytic leukemia: report of a case and review of literature.International journal of clinical and experimental pathology · 2015Review
- 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
- 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
- T-cell and natural killer-cell large granular lymphocyte leukemia neoplasias.Leukemia & lymphoma · 2011Review
- Dynamical and structural analysis of a T cell survival network identifies novel candidate therapeutic targets for large granular lymphocyte leukemia.PLoS computational biology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
T-cell large granular lymphocytic leukemia (T-LGL) is characterized by chronic clonal lymphoproliferation of cytotoxic T lymphocytes (CTLs). Despite exhibiting phenotypic properties of antigen-activated cells, including expression of Fas and FasL, T-LGL cells accumulate and demonstrate resistance to apoptosis. We propose that increased activity of a prosurvival signaling pathway in T-LGL is responsible for attenuated apoptosis in T-LGL. Given the importance of the phosphatidylinositol-3 kinase (PI3K)-AKT pathway in regulating the balance between survival and apoptosis, we analyzed AKT activity in T-LGL cells. Compared with resting CTLs from healthy donors, patients' T-LGL cells showed higher levels of phosphorylated AKT. We demonstrate that phospho-AKT induction is dependent on the upstream activity of a Src family kinase. Since the PI3K-AKT pathway can antagonize the ability of Fas to initiate apoptosis, we hypothesized that inhibition of PI3K would lead to reacquisition of Fas sensitivity in T-LGL. Inhibition of the PI3K-AKT pathway alone led to brisk spontaneous apoptosis of T-LGL. These results suggest that T-LGL pathogenesis is dependent on activity of the PI3K-AKT pathway, without which the leukemic cells will begin to undergo spontaneous apoptosis. We propose that novel therapeutics inhibiting the PI3K-AKT axis may provide effective treatment for T-LGL.
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What OpenQuestion holds
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.