ArticleCell death and differentiation2010
Inhibition of Lck enhances glucocorticoid sensitivity and apoptosis in lymphoid cell lines and in chronic lymphocytic leukemia.
Article in Cell death and differentiation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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
35 citing papers in PubMed, 65 citations in OpenAlex.
- UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia.Life science alliance · 2025Article
- SMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor-T Cells Proliferation Through PI3K/Akt Signaling Pathway.Journal of cellular physiology · 2025Article
- All-photonic kinase inhibitors: light-controlled release-and-report inhibition.Chemical science · 2024Article
- PBMC-engrafted humanized mice models for evaluating immune-related and anticancer drug delivery systems.Frontiers in molecular biosciences · 2024Review
- Review
- Heat-Shock Proteins in Leukemia and Lymphoma: Multitargets for Innovative Therapeutic Approaches.Cancers · 2023Review
- A Novel Peptide that Disrupts the Lck-IPArchives of microbiology & immunology · 2023Article
- New insights into the Lck-NF-κB signaling pathway.Frontiers in cell and developmental biology · 2023Review
- Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia.Science advances · 2022Article
- Integrative and Comprehensive Pan-Cancer Analysis of Lymphocyte-Specific Protein Tyrosine Kinase in Human Tumors.International journal of molecular sciences · 2022Article
- Effects of glucocorticoids on leukocytes: Genomic and non-genomic mechanisms.World journal of clinical cases · 2022Review
- New horizons in drug discovery of lymphocyte-specific protein tyrosine kinase (Lck) inhibitors: a decade review (2011-2021) focussing on structure-activity relationship (SAR) and docking insights.Journal of enzyme inhibition and medicinal chemistry · 2021Review
- Combination efficacy of ruxolitinib with standard-of-care drugs in CRLF2-rearranged Ph-like acute lymphoblastic leukemia.Leukemia · 2021Article
- Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia.Haematologica · 2021Article
- LCK and CD3E Orchestrate the Tumor Microenvironment and Promote Immunotherapy Response and Survival of Muscle-Invasive Bladder Cancer Patients.Frontiers in cell and developmental biology · 2021Article
- Beyond TCR Signaling: Emerging Functions of Lck in Cancer and Immunotherapy.International journal of molecular sciences · 2019Review
- Silencing of COPB2 inhibits the proliferation of gastric cancer cells and induces apoptosis via suppression of the RTK signaling pathway.International journal of oncology · 2019Article
- Ectopic Lck expression in CLL demarcates intratumoral subpopulations with aberrant B-cell receptor signaling.Blood advances · 2018Article
- Antitumor activity of antibody against cytotoxic T lymphocyte epitope peptide of lymphocyte-specific protein tyrosine kinase.Cancer science · 2018Article
- Lck is a relevant target in chronic lymphocytic leukaemia cells whose expression variance is unrelated to disease outcome.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Glucocorticoids are used as part of front-line therapy to treat lymphoid malignancy because of their remarkable ability to induce apoptosis. Yet, in T cells, glucocorticoid-induced apoptosis is readily inhibited by lymphocyte activation and signaling. We have previously shown that the Src family kinase, Lck (lymphocyte cell-specific tyrosine kinase), which is predominantly expressed in T cells, interacts with IP3 receptors to facilitate calcium signaling. Here, we discovered that dexamethasone downregulates Lck, which, in turn, suppresses lymphocyte activation by inhibiting pro-survival calcium oscillations. Moreover, stable expression of shRNAs that selectively targeted Lck or treatment with the Src inhibitor dasatinib (BMS-354825) enhanced apoptosis induction by dexamethasone. To investigate the effect of Lck inhibition in a primary leukemia model, we employed chronic lymphocytic leukemia (CLL) cells that aberrantly expressed Lck and were relatively insensitive to dexamethasone. Lck expression was correlated with resistance to dexamethasone in CLL cells, and its inhibition by dasatinib or other inhibitors markedly enhanced glucocorticoid sensitivity. Collectively, these data indicate that Lck protects cells from glucocorticoid-induced apoptosis and its inhibition enhances sensitivity to dexamethasone. Small-molecule inhibitors of Lck, such as dasatinib, may function to reverse glucocorticoid resistance in some lymphoid malignancies.
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.