ArticleOncotarget2018
CXCR4- and BCR-triggered integrin activation in B-cell chronic lymphocytic leukemia cells depends on JAK2-activated Bruton's tyrosine kinase.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed.
- 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
- Article
- Nanomechanical and Thermodynamic Alterations of Red Blood Cells in Chronic Lymphocytic Leukemia: Implications for Disease and Treatment Monitoring.International journal of molecular sciences · 2025Article
- The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Review
- Review
- Aberrantly Expressed Mitochondrial Lipid Kinase, AGK, Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Tumor cells escape immunosurveillance by hampering LFA-1.Frontiers in immunology · 2025Review
- Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?Cancers · 2024Review
- Lymphocyte migration and retention properties affected by ibrutinib in chronic lymphocytic leukemia.Haematologica · 2024Article
- Identification of the Axis β-Catenin-BTK in the Dynamic Adhesion of Chronic Lymphocytic Leukemia Cells to Their Microenvironment.International journal of molecular sciences · 2023Article
- The Role of the Microenvironment and Cell Adhesion Molecules in Chronic Lymphocytic Leukemia.Cancers · 2023Review
- Concomitant targeting of FLT3 and BTK overcomes FLT3 inhibitor resistance in acute myeloid leukemia through the inhibition of autophagy.Haematologica · 2023Article
- 2-Arachidonoylglycerol Modulates CXCL12-Mediated Chemotaxis in Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia.Cancers · 2023Article
- Research-based flow cytometry assays for pathogenic assessment in the human B-cell biology of gene variants revealed in the diagnosis of inborn errors of immunity: a Bruton's tyrosine kinase case-study.Frontiers in immunology · 2023Article
- Changes in the BTK/NF-κB signaling pathway and related cytokines in different stages of neuromyelitis optica spectrum disorders.European journal of medical research · 2022Article
- A Comprehensive Review of Receptor-Type Tyrosine-Protein Phosphatase Gamma (PTPRG) Role in Health and Non-Neoplastic Disease.Biomolecules · 2022Review
- Calcium-dependent signalling in B-cell lymphomas.Oncogene · 2021Review
- The Role of the Tumor Suppressor Gene Protein Tyrosine Phosphatase Gamma in Cancer.Frontiers in cell and developmental biology · 2021Review
- Oncogenic Mutations of MYD88 and CD79B in Diffuse Large B-Cell Lymphoma and Implications for Clinical Practice.Cancers · 2020Review
- VLA-4 Expression and Activation in B Cell Malignancies: Functional and Clinical Aspects.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bruton's tyrosine kinase (BTK) regulates the B-cell receptor (BCR) signaling pathway, which, in turn, plays a critical role in B-cell chronic lymphocytic leukemia (B-CLL) pathogenesis. The BTK-specific inhibitor Ibrutinib blocks BCR signaling and is now approved as effective B-CLL therapy. Chemokines, such as the homeostatic chemokine CXCL12, play a central role in B-CLL pathogenesis and progression, by regulating CLL cell interaction with the stromal microenvironment, leading to cells survival and proliferation. In this study, we investigated, in normal versus CLL B-lymphocytes, the role of BTK in signal transduction activated by the CXCL12-CXCR4 signaling axis and its involvement in rapid integrin activation. We show that BTK is rapidly activated by CXCL12 in healthy as well as CLL B-lymphocytes, with a kinetic of tyr-phosphorylation coherent with rapid adhesion triggering. BTK inhibition prevents CXCL12-induced triggering of lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4) integrins. Furthermore, BTK inhibition blocks the activation of the small GTP-binding protein RhoA, controlling integrin affinity. Very importantly, we show that BTK tyr-phosphorylation and activation by CXCL12 depends on upstream activation of JAK2 tyrosine kinase. A comparative analysis of 36 B-CLL patients demonstrates that JAK2-dependent BTK regulatory role on integrin activation by CXCL12 is fully conserved in CLL cells. Finally, we show that the JAK2-BTK axis also regulates signaling to integrin activation by BCR. Thus, BTK and JAK protein tyrosine kinases (PTKs) manifest a hierarchical activity both in chemokine- as well as BCR-mediated integrin activation and dependent adhesion, potentially suggesting the possibility of combined therapeutic approaches to B-CLL treatment.
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.