ArticleLeukemia2014
BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 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
108 citing papers in PubMed, 184 citations in OpenAlex.
- Pharmacodynamic Analysis of BTK Inhibition in Patients with Chronic Lymphocytic Leukemia Treated with Acalabrutinib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Ibrutinib therapy downregulates AID enzyme and proliferative fractions in chronic lymphocytic leukemia.Blood · 2019Trial
- Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study.Blood · 2018Trial
- Trial
- Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.PloS one · 2016Trial
- Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial.The Lancet. Oncology · 2015Trial
- Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.Leukemia · 2014Trial
- Trial
- BTK inhibition enhances immunovirotherapy in glioblastoma via tertiary lymphoid structure modulation.bioRxiv : the preprint server for biology · 2026Article
- Structure-guided discovery of a novel BTK inhibitor inducing apoptosis and G1 phase arrest in tumor cells.Molecular diversity · 2026Article
- B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma.Cell communication and signaling : CCS · 2025Review
- Shelter in place: live CLL cells inside the bone marrow fibroblasts and its implication in residual disease persistence.Blood neoplasia · 2025Article
- Comprehensive comparison of enzymatic and bisulfite DNA methylation analysis in clinically relevant samples.Clinical epigenetics · 2025Article
- The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Review
- Immunohistochemical Study of the Localization of Ibrutinib-Protein Conjugates in the Rat Gastrointestinal Tract.Acta histochemica et cytochemica · 2025Article
- A Case Series and Literature Review on Zanubrutinib Therapy for the Treatment of Relapsed/Refractory Immune Thrombocytopenia.Cancer reports (Hoboken, N.J.) · 2025Review
- A Bruton tyrosine kinase inhibitor-resistance gene signature predicts prognosis and identifies TRIP13 as a potential therapeutic target in diffuse large B-cell lymphoma.Scientific reports · 2024Article
- Ibrutinib sensitizes CLL cells to venetoclax by interrupting TLR9-induced CD40 upregulation and protein translation.Leukemia · 2023Article
- Resistance to Bruton tyrosine kinase inhibition in chronic lymphocytic leukaemia and non-Hodgkin lymphoma.British journal of haematology · 2023Review
- Overexpression of Bruton Tyrosine Kinase Inhibits the Proliferation, Migration, and Invasion of Non-Small Cell Lung Cancer Cells.Analytical cellular pathology (Amsterdam) · 2023Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bruton agammaglobulinemia tyrosine kinase (BTK), a cytoplasmic protein tyrosine kinase, is a component of the B-cell receptor signaling pathway. Ibrutinib, a BTK inhibitor, has demonstrated a significant clinical activity against chronic lymphocytic leukemia (CLL) in early clinical trials. Understanding the molecular mechanisms of action would shed light on CLL pathophysiology and provide additional opportunities for the development of new therapies. In this study, we have chosen an in vivo approach by employing an ongoing phase 1b trial of ibrutinib. We prospectively collected and analyzed serial samples from the CLL patients before and after the initiation of ibrutinib. We found that the blockage of cell proliferation was one of the primary effects of ibrutinib against leukemic CLL cells in vivo. Using a co-culture system that induces CLL proliferation in vitro, analysis of several parameters, including Ki-67 expression and bromodeoxyuridine (BrdU) incorporation, revealed that the proliferation of CLL cells was directly inhibited by ibrutinib. Furthermore, activities of BTK and phospholipase Cγ2 as well as downstream signaling molecules, AKT and ERK, were all coordinately downregulated over time in ibrutinib-treated patients. Our findings suggest that the cell proliferation is one of the essential properties of CLL. Blocking cell proliferation via inhibition of BTK-mediated signaling may contribute to clinical responses in ibrutinib-treated patients.
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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.