ArticleFrontiers in oncology2023
Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinib
Article in Frontiers in oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- High-content imaging of primary chronic lymphocytic leukemia cells predicts patient cohorts with distinct cellular drug responses.iScience · 2025Article
- Effect of statins on IL-10 signaling and production by chronic lymphocytic leukemia cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Impact of Tyrosine Kinase Inhibitors on the Expression Pattern of Epigenetic Regulators.Cancers · 2025Article
- IL-1 receptor antagonism reveals a yin-yang relationship between NFκB and interferon signaling in chronic lymphocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
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Abstract
Introduction: Chronic lymphocytic leukemia (CLL) is characterized by an aberrant cytokine network that can support tumor growth by triggering janus kinase (JAK)/STAT pathways. Targeting cytokine-signaling should then be a rational therapeutic strategy but the JAK inhibitor ruxolitinib failed to control and seemingly accelerated the disease in clinical trials. Methods: The effect of ruxolitinib on primary human CLL cells was studied Results: Ruxolitinib increased phosphorylation of IRAK4, an important toll-like receptor (TLR)- signaling intermediate, in circulating CLL cells Discussion: These findings suggest the possible benefits of inhibiting growth factors with JAK inhibitors in CLL are outweighed by negative effects on potential tumor suppressors such as IL-10 that allow unrestrained activation of NFκB by drivers such as TLRs. Specific inhibition of growth-promoting cytokines with blocking antibodies or infusing suppressive cytokines like IL-10 might be better strategies to manipulate cytokines in CLL.
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Registered trials
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