ArticleLeukemia2016
Calcineurin and GSK-3 inhibition sensitizes T-cell acute lymphoblastic leukemia cells to apoptosis through X-linked inhibitor of apoptosis protein degradation.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- PMSA as a potential modulator of calcineurin phosphatase activity.Scientific reports · 2026Article
- A Review on Picrosides Targeting NFκB and its Proteins for Treatment of Breast Cancer.Cell biochemistry and biophysics · 2024Review
- Identification of an Epi-metabolic dependency on EHMT2/G9a in T-cell acute lymphoblastic leukemia.Cell death & disease · 2022Article
- Inhibition of Noncanonical CaNeurochemical research · 2022Article
- Anticancer effect of Indanone-based thiazolyl hydrazone derivative on p53 mutant colorectal cancer cell lines: AnFrontiers in oncology · 2022Article
- GSK-3: a multifaceted player in acute leukemias.Leukemia · 2021Review
- Responsiveness to Hedgehog Pathway Inhibitors in T-Cell Acute Lymphoblastic Leukemia Cells Is Highly Dependent on 5'AMP-Activated Kinase Inactivation.International journal of molecular sciences · 2021Article
- Lithium and Therapeutic Targeting of GSK-3.Cells · 2021Review
- Inhibition of XIAP increases carboplatin sensitivity in ovarian cancer.OncoTargets and therapy · 2018Article
- Role of the NFκB-signaling pathway in cancer.OncoTargets and therapy · 2018Review
- Aberrant Signaling Pathways in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2017Review
- Pharmacophore-based screening and drug repurposing exemplified on glycogen synthase kinase-3 inhibitors.Molecular diversity · 2017Article
- Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The calcineurin (Cn)-nuclear factor of activated T cells signaling pathway is critically involved in many aspects of normal T-cell physiology; however, its direct implication in leukemogenesis is still ill-defined. Glycogen synthase kinase-3β (GSK-3β) has recently been reported to interact with Cn in neuronal cells and is implicated in MLL leukemia. Our biochemical studies clearly demonstrated that Cn was able to interact with GSK-3β in T-cell acute lymphoblastic leukemia (T-ALL) cells, and that this interaction was direct, leading to an increased catalytic activity of GSK-3β, possibly through autophosphorylation of Y216. Sensitivity to GSK-3 inhibitor treatment correlated with altered GSK-3β phosphorylation and was more prominent in T-ALL with Pre/Pro immunophenotype. In addition, dual Cn and GSK-3 inhibitor treatment in T-ALL cells promoted sensitization to apoptosis through proteasomal degradation of X-linked inhibitor of apoptosis protein (XIAP). Consistently, resistance to drug treatments in primary samples was strongly associated with higher XIAP protein levels. Finally, we showed that dual Cn and GSK-3 inhibitor treatment in vitro and in vivo is effective against available models of T-ALL, indicating an insofar untapped therapeutic opportunity.
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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.