ArticlePloS one2013
Role of CTLA4 in the proliferation and survival of chronic lymphocytic leukemia.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- The prognostic value of cytotoxic T-lymphocyte antigen 4 in cancers: a systematic review and meta-analysis.Scientific reports · 2017Pooled it
- Targeting LRBA triggers CTLA4 degradation and antitumor immunity for cancer immunotherapy.Nature communications · 2025Article
- CTLA-4 silencing could promote anti-tumor effects in hepatocellular.Medical oncology (Northwood, London, England) · 2024Article
- Aberrant spliceosome activity via elevated intron retention and upregulation and phosphorylation of SF3B1 in chronic lymphocytic leukemia.Molecular therapy. Nucleic acids · 2024Article
- Current Understanding of PCSK9 and Its Relevance to Cancer Prognosis and Immune Therapy: A Review.Iranian journal of pathology · 2024Review
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- Current Approaches of Immune Checkpoint Therapy in Chronic Lymphocytic Leukemia.Current treatment options in oncology · 2023Review
- Subgroup-specific gene expression profiles and mixed epistasis in chronic lymphocytic leukemia.Haematologica · 2023Article
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- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) as an undetermined tool in tumor cells.Human cell · 2023Review
- Concurrent development of small lymphocytic lymphoma and lung cancer: A report of two cases and a review of the literature.Journal of clinical and experimental hematopathology : JCEH · 2023Review
- Multi-targeted immunotherapeutics to treat B cell malignancies.Journal of controlled release : official journal of the Controlled Release Society · 2023Review
- Differential regulation of CTLA4 expression through BTK-dependent and independent mechanisms in CLL.Blood advances · 2022Article
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- Identification and validation of the role of c-Myc in head and neck squamous cell carcinoma.Frontiers in oncology · 2022Article
- Comparison of Laboratory Methods for the Clinical Follow Up of Checkpoint Blockade Therapies in Leukemia: Current Status and Challenges Ahead.Frontiers in oncology · 2022Review
- Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Distinctive Signaling Profiles With Distinct Biological and Clinical Implications in Aggressive CLL Subsets With Stereotyped B-Cell Receptor Immunoglobulin.Frontiers in oncology · 2021Review
- Cytotoxic T lymphocyte antigen-4 (CTLA-4) expression in chordoma and tumor-infiltrating lymphocytes (TILs) predicts prognosis of spinal chordoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Article
- Seven immune-related genes prognostic power and correlation with tumor-infiltrating immune cells in hepatocellular carcinoma.Cancer medicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Earlier, we reported that CTLA4 expression is inversely correlated with CD38 expression in chronic lymphocytic leukemia (CLL) cells. However, the specific role of CTLA4 in CLL pathogenesis remains unknown. Therefore, to elucidate the possible role of CTLA4 in CLL pathogenesis, CTLA4 was down-regulated in primary CLL cells. We then evaluated proliferation/survival in these cells using MTT, (3)H-thymidine uptake and Annexin-V apoptosis assays. We also measured expression levels of downstream molecules involved in B-cell proliferation/survival signaling including STAT1, NFATC2, c-Fos, c-Myc, and Bcl-2 using microarray, PCR, western blotting analyses, and a stromal cell culture system. CLL cells with CTLA4 down-regulation demonstrated a significant increase in proliferation and survival along with an increased expression of STAT1, STAT1 phosphorylation, NFATC2, c-Fos phosphorylation, c-Myc, Ki-67 and Bcl-2 molecules. In addition, compared to controls, the CTLA4-downregulated CLL cells showed a decreased frequency of apoptosis, which also correlated with increased expression of Bcl-2. Interestingly, CLL cells from lymph node and CLL cells co-cultured on stroma expressed lower levels of CTLA4 and higher levels of c-Fos, c-Myc, and Bcl-2 compared to CLL control cells. These results indicate that microenvironment-controlled-CTLA4 expression mediates proliferation/survival of CLL cells by regulating the expression/activation of STAT1, NFATC2, c-Fos, c-Myc, and/or Bcl-2.
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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.