ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Autocrine Signaling by Wnt-5a Deregulates Chemotaxis of Leukemic Cells and Predicts Clinical Outcome in Chronic Lymphocytic Leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 55 citations in OpenAlex.
- Casein kinase 1δ/ε inhibition suppresses CLL proliferation through cell-intrinsic and microenvironmental mechanisms.HemaSphere · 2026Article
- Role of the Ror family receptors in Wnt5a signaling.In vitro cellular & developmental biology. Animal · 2024Review
- Prognostic Value of the Expression of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR-1) in Chronic Lymphocytic Leukemia.International journal of hematology-oncology and stem cell research · 2023Article
- Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile ofEpigenetics · 2022Article
- ROR1: an orphan becomes apparent.Blood · 2022Review
- Evaluation of miRNA 223/125a and COBLL1 Expressions and ROR-1 Levels as Reliable Markers in B- chronic Lymphocytic Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Immunoglobulin Gene Sequence as an Inherited and Acquired Risk Factor for Chronic Lymphocytic Leukemia.Cancers · 2022Review
- Genetic Biomarkers and Their Clinical Implications in B-Cell Acute Lymphoblastic Leukemia in Children.International journal of molecular sciences · 2022Review
- Aberrantly expressed Wnt5a in nurse-like cells drives resistance to Venetoclax in chronic lymphocytic leukemia.Cell death discovery · 2022Article
- Lyn Phosphorylates and Controls ROR1 Surface Dynamics During Chemotaxis of CLL Cells.Frontiers in cell and developmental biology · 2022Article
- Role of casein kinase 1 in the amoeboid migration of B-cell leukemic and lymphoma cells: A quantitative live imaging in the confined environment.Frontiers in cell and developmental biology · 2022Article
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- Article
- Frizzled Receptors in Tumors, Focusing on Signaling, Roles, Modulation Mechanisms, and Targeted Therapies.Oncology research · 2021Review
- Review
- WNT5B in Physiology and Disease.Frontiers in cell and developmental biology · 2021Review
- Targeting the Receptor Tyrosine Kinase ROR1 by Small Molecules.Handbook of experimental pharmacology · 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
- Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies.Frontiers in oncology · 2021Review
- Targeting Casein Kinase 1 (CK1) in Hematological Cancers.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
purposeROR1, a receptor in the noncanonical Wnt/planar cell polarity (PCP) pathway, is upregulated in malignant B cells of chronic lymphocytic leukemia (CLL) patients. It has been shown that the Wnt/PCP pathway drives pathogenesis of CLL, but which factors activate the ROR1 and PCP pathway in CLL cells remains unclear. EXPERIMENTAL
designB lymphocytes from the peripheral blood of CLL patients were negatively separated using RosetteSep (StemCell) and gradient density centrifugation. Relative expression of WNT5A, WNT5B, and ROR1 was assessed by quantitative real-time PCR. Protein levels, protein interaction, and downstream signaling were analyzed by immunoprecipitation and Western blotting. Migration capacity of primary CLL cells was analyzed by the Transwell migration assay.
resultsBy analyzing the expression in 137 previously untreated CLL patients, we demonstrate that WNT5A and WNT5B genes show dramatically (five orders of magnitude) varying expression in CLL cells. High WNT5A and WNT5B expression strongly associates with unmutated IGHV and shortened time to first treatment. In addition, WNT5A levels associate, independent of IGHV status, with the clinically worst CLL subgroups characterized by dysfunctional p53 and mutated SF3B1. We provide functional evidence that WNT5A-positive primary CLL cells have increased motility and attenuated chemotaxis toward CXCL12 and CCL19 that can be overcome by inhibitors of Wnt/PCP signaling.
conclusionsThese observations identify Wnt-5a as the crucial regulator of ROR1 activity in CLL and suggest that the autocrine Wnt-5a signaling pathway allows CLL cells to overcome natural microenvironmental regulation.
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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.