ArticleThe Journal of experimental medicine2018
Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia.
Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 92 citations in OpenAlex.
- Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Development and Validation of a Four-Factor Prognostic Model.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Trial
- Review
- From Time-Limited Therapy to Treatment-Free Observation: The Evolving Role of MRD in CLL Management.European journal of haematology · 2026Review
- CD49d governs immune synapse formation through actin rearrangements and synchronizes BCR signaling in CLL.Blood · 2026Article
- No lymphocytosis increase after cBTKi is a rare phenomenon except for CD49d-positive CLL mainly expressed in trisomy 12.Blood advances · 2026Article
- Real-world safety and effectiveness of zanubrutinib vs ibrutinib in CLL: the CLL-ZANU2024 Italian cohort.Blood advances · 2026Article
- The cytoskeletal control of B cell receptor and integrin signaling in normal B cells and chronic lymphocytic leukemia.FEBS letters · 2025Review
- Article
- Dynamic stimulation promotes functional tissue-like organization of a 3D human lymphoid microenvironment model in vitro.Cell reports methods · 2025Article
- Resistance mechanisms and approach to chronic lymphocytic leukemia after BTK inhibitor therapy.Leukemia & lymphoma · 2025Review
- Evaluation of Constitutive or Induced Activation State of the VLA-4 Integrin in Human and Murine Samples.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Neutrophils in the Spotlight-An Analysis of Neutrophil Function and Phenotype in ARDS.International journal of molecular sciences · 2024Article
- Article
- Early reappearance of intraclonal proliferative subpopulations in ibrutinib-resistant chronic lymphocytic leukemia.Leukemia · 2024Article
- Article
- Lymphocyte migration and retention properties affected by ibrutinib in chronic lymphocytic leukemia.Haematologica · 2024Article
- Ibrutinib and the chemotactic lymph node choreography.Haematologica · 2024Article
- CD49d in chronic lymphocytic leukemia: a molecule with multiple regulation layers. Comment to "Sialylation regulates migration in chronic lymphocytic leukemia".Haematologica · 2024Article
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Authors and funding
29 authors at 10 institutions in 3 countries.
Funding
Abstract
The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors.
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