ArticleThe Journal of clinical investigation2001
Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 289 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
289 citing papers in PubMed, 1 synthesis or guideline pooled it, 642 citations in OpenAlex.
- The Radiosensitizing Potentials of Silymarin/Silibinin in Cancer: A Systematic Review.Current medicinal chemistry · 2024Pooled it
- Alemtuzumab in T-cell large granular lymphocytic leukaemia: interim results from a single-arm, open-label, phase 2 study.The Lancet. Haematology · 2016Trial
- Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998).Leukemia · 2015Trial
- Review
- Anti-PAD4 antibodies link autoimmunity to PAD4 with CTL-associated rheumatoid arthritis.Annals of the rheumatic diseases · 2026Article
- Vitamin D Deficiency in Leukemia: Implications for Pathophysiology, Treatment, and Supportive Care.Nutrients · 2026Review
- Superior response and survival of intensive chemotherapy over venetoclax plus azacitidine in newly diagnosed KIT-mutated acute myeloid leukemia.Annals of hematology · 2026Article
- Ginsenoside Rc mitigates hippocampal neuronal damage and cognitive impairment in vascular dementia rats via the pY705-Stat3/Foxo3a and pS727-Stat3/GRIM-19 pathways.Journal of ginseng research · 2025Article
- Transcriptomic landscape of CD8+ and CD4 + T-LGL leukemia revealed the distinct impact of STAT3 and STAT5B activating mutations.Leukemia · 2025Article
- Synergistic MDM2-STAT3 Inhibition Demonstrates Strong Anti-Leukemic Efficacy in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Article
- Brigimadlin (BI-907828) and napabucasin (BBI608) cooperatively trigger apoptosis in chronic lymphocytic leukemia cells by simultaneous iİnhibition of MDM2 and STAT3.Molecular biology reports · 2025Article
- Epidemiology, Survival, and Second Primary Malignancies in T-Cell Large Granular Lymphocytic Leukemia.EJHaem · 2025Article
- Functional apoptosis profiling reveals vulnerabilities in T-cell large granular lymphocytic leukemia.Annals of hematology · 2025Article
- Inhibition of miR-20a promotes neural stem cell survival under oxidative stress conditions.Frontiers in neuroscience · 2025Article
- Large granular lymphocyte leukemia: a clonal disorder with autoimmune manifestations.Hematology. American Society of Hematology. Education Program · 2024Review
- Review
- Refractory pure red cell aplasia associated with T-cell large granular lymphocyte leukemia treated by ruxolitinib.Annals of hematology · 2024Article
- Article
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- Large Granular Lymphocytic Leukemia: Clinical Features, Molecular Pathogenesis, Diagnosis and Treatment.Cancers · 2024Review
229 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Large granular lymphocyte (LGL) leukemia is characterized by the expansion of antigen-activated cytotoxic T lymphocytes. These leukemic cells are resistant to Fas-mediated apoptosis despite expressing high levels of Fas. We found that leukemic LGL from 19 patients displayed high levels of activated STAT3. Treatment of leukemic LGL with the JAK-selective tyrosine kinase inhibitor AG-490 induced apoptosis with a corresponding decrease in STAT-DNA binding activity. Moreover, using an antisense oligonucleotide approach to diminish STAT3 expression, we found that Fas sensitivity was restored in leukemic LGL. AG-490-induced apoptosis in leukemic LGL was independent of Bcl-xL or Bcl-2 expression. However, we found that the Bcl-2-family protein Mcl-1 was significantly reduced by AG-490 treatment. Activated STAT3 was shown to bind an SIE-related element in the murine mcl-1 promoter. Using a luciferase reporter assay, we demonstrated that v-src overexpression in NIH3T3 induced STAT3-dependent transcriptional activity from the mcl-1 promoter and increased endogenous Mcl-1 protein levels. We conclude that STAT3 activation contributed to accumulation of the leukemic LGL clones. These findings suggest that investigation should focus on novel strategies targeting STAT3 in the treatment of LGL leukemia.
Indexed as
Identifiers
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.