ArticleOncotarget2015
CXCL12-induced VLA-4 activation is impaired in trisomy 12 chronic lymphocytic leukemia cells: a role for CCL21.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- The cytoskeletal control of B cell receptor and integrin signaling in normal B cells and chronic lymphocytic leukemia.FEBS letters · 2025Review
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- Effect of ibrutinib on CCR7 expression and functionality in chronic lymphocytic leukemia and its implication for the activity of CAP-100, a novel therapeutic anti-CCR7 antibody.Cancer immunology, immunotherapy : CII · 2022Article
- C-C Chemokine Receptor 7 in Cancer.Cells · 2022Review
- Molecular Systems Architecture of Interactome in the Acute Myeloid Leukemia Microenvironment.Cancers · 2022Review
- CD44 engagement enhances acute myeloid leukemia cell adhesion to the bone marrow microenvironment by increasing VLA-4 avidity.Haematologica · 2021Article
- Of Lymph Nodes and CLL Cells: Deciphering the Role of CCR7 in the Pathogenesis of CLL and Understanding Its Potential as Therapeutic Target.Frontiers in immunology · 2021Review
- Drug repurposing for targeting cyclic nucleotide transporters in acute leukemias - A missed opportunity.Seminars in cancer biology · 2021Review
- CCR7 in Blood Cancers - Review of Its Pathophysiological Roles and the Potential as a Therapeutic Target.Frontiers in oncology · 2021Review
- Importance of Crosstalk Between Chronic Lymphocytic Leukemia Cells and the Stromal Microenvironment: Direct Contact, Soluble Factors, and Extracellular Vesicles.Frontiers in oncology · 2020Review
- Microenvironment-induced CD44v6 promotes early disease progression in chronic lymphocytic leukemia.Blood · 2018Article
- Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia.The Journal of experimental medicine · 2018Article
- Combined CXCR3/CXCR4 measurements are of high prognostic value in chronic lymphocytic leukemia due to negative co-operativity of the receptors.Haematologica · 2016Article
- BCAT1 expression associates with ovarian cancer progression: possible implications in altered disease metabolism.Oncotarget · 2015Article
- Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 4 countries.
Funding
Abstract
Homing to distinct lymphoid organs enables chronic lymphocytic leukemia (CLL) cells to receive pro-survival and proliferative signals. Cytogenetic aberrations can significantly affect CLL cell compartmentalization. Trisomy 12 (tri12) defines a CLL subgroup with specific clinical features and increased levels of the negative prognostic marker CD49d, the α4-subunit of the integrin VLA-4, which is a key regulator of CLL cell homing to bone marrow (BM). Chemokine-induced inside-out VLA-4 activation, particularly via the CXCL12-CXCR4 axis, increases the arrest of various cell types on VCAM-1 presenting endothelium. Here, we demonstrate that high CD49d expression in tri12 CLL is accompanied by decreased CXCR4 expression. Dissecting functional consequences of these alterations, we observed that tri12 CLL cell homing to murine BM is not affected by CXCR4-CXCL12 blockage using AMD3100 or olaptesed pegol/NOX-A12. In line, CCL21-CCR7 rather than CXCL12-CXCR4 interactions triggered VLA-4-mediated arrests of tri12 CLL cells to VCAM-1 under blood flow conditions. Concordantly, in real-time kinetic analyses we found CCL21 but not CXCL12 being capable to induce inside-out VLA-4 conformational changes in this CLL subgroup. Our results provide novel insights into the peculiar clinico-biological behaviour of tri12 CLL and emphasize its specific chemokine and integrin utilization during pathophysiologically and therapeutically relevant interactions with the microenvironment.
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