ArticleLeukemia2016
BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
What it found
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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.
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Who cites it
122 citing papers in PubMed, 183 citations in OpenAlex.
- Docirbrutinib is a pan-mutant BTK inhibitor and inhibits B-cell receptor signaling in chronic lymphocytic leukemia cells in preclinical and early clinical investigations.Blood cancer journal · 2026Trial
- A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia.Blood · 2018Trial
- Ibrutinib treatment improves T cell number and function in CLL patients.The Journal of clinical investigation · 2017Trial
- Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.PloS one · 2016Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- STAT3 as a Candidate Shared Regulator of the CXCR4/CXCL12 and CXCR5/CXCL13 Homing Axes in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2026Review
- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- Mechanisms of resistance to bruton's tyrosine kinase inhibitors: synergistic effects of tumor microenvironment regulation and signaling pathways.Annals of hematology · 2026Review
- BTK Inhibition in Hematology: From CLL/SLL to Emerging Applications Across B-Cell and Immune Disorders.Biomolecules · 2026Review
- Tonic signaling of the B-cell antigen-specific receptor is a common functional hallmark in chronic lymphocytic leukemia cell phosphoproteomes at early disease stages.Molecular oncology · 2025Article
- Shelter in place: live CLL cells inside the bone marrow fibroblasts and its implication in residual disease persistence.Blood neoplasia · 2025Article
- Bruton tyrosine kinase covalent inhibition shapes the immune microenvironment in chronic lymphocytic leukemia.Haematologica · 2025Article
- Wnt5a induces ROR1 dependent NF-κB activation to enhance MMP-9 expression and invasiveness in chronic lymphocytic leukemia.Leukemia · 2025Article
- Functional proteoform group deconvolution reveals a broader spectrum of ibrutinib off-targets.Nature communications · 2025Article
- Bruton's Tyrosine Kinase Inhibitors: A Versatile Therapeutic Approach for Cancer, Autoimmune Disorders, GVHD and COVID-19.Mini reviews in medicinal chemistry · 2025Review
- Transcriptomic clustering of chronic lymphocytic leukemia: molecular subtypes based on Bruton's tyrosine kinase expression levels.Blood cancer journal · 2024Article
- Bruton Tyrosine Kinase Inhibition Decreases Inflammation and Differentially Impacts Phagocytosis and Cellular Metabolism in Mouse- and Human-derived Myeloid Cells.ImmunoHorizons · 2024Article
- Ibrutinib and venetoclax in combination for chronic lymphocytic leukemia: synergy in practice.Blood neoplasia · 2024Article
- Early reappearance of intraclonal proliferative subpopulations in ibrutinib-resistant chronic lymphocytic leukemia.Leukemia · 2024Article
- Pim Kinase Inhibition Disrupts CXCR4 Signalling in Megakaryocytes and Platelets by Reducing Receptor Availability at the Surface.International journal of molecular sciences · 2024Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Bruton's tyrosine kinase (BTK) is involved in the regulation of B-cell growth, migration and adhesion. The importance of BTK in cell trafficking is emphasized by the clonal contraction proceeded by lymphocytosis typical for the enzyme inhibitor, ibrutinib, in B-cell malignancies, including chronic lymphocytic leukemia (CLL). Here, we investigated BTK regulation of leukemic B-cell trafficking in a mouse model of aggressive TCL1 CLL-like disease. Inhibiting BTK by ibrutinib reduced surface membrane (sm) levels of CXCR4 but not CXCR5, CD49d and other adhesion/homing receptors. Decreased smCXCR4 levels resulted from blocking receptor signal transduction, which in turn aborted cycling from and to the membrane. This resulted in rapid re-distribution of CLL cells from spleens and lymph nodes into the circulation. CLL cells with impaired smCXCR4 from BTK inhibition failed to home to spleens. These functional changes mainly resulted from inhibition of CXCR4 phosphorylation at Ser339, mediated directly by blocking BTK enzymatic activity and indirectly by affecting the function of downstream targets PLCγ2 and PKCμ, and eventually synthesis of PIM-1 and BTK itself. Our data identify CXCR4 as a key regulator in BTK-mediated CLL-cell retention and have elucidated a complex set of not previously described mechanisms responsible for these effects.
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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.