ArticleJournal of cellular and molecular medicine2018
Microenvironment-induced PIM kinases promote CXCR4-triggered mTOR pathway required for chronic lymphocytic leukaemia cell migration.
Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Pim Kinase Inhibition Disrupts CXCR4 Signalling in Megakaryocytes and Platelets by Reducing Receptor Availability at the Surface.International journal of molecular sciences · 2024Article
- SIRT1 and HSP90α feed-forward circuit safeguards chromosome segregation integrity in diffuse large B cell lymphomas.Cell death & disease · 2023Article
- Profiling of basal and ligand-dependent GPCR activities by means of a polyvalent cell-based high-throughput platform.Nature communications · 2023Article
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- PIM3 kinase promotes tumor metastasis in hepatoblastoma by upregulating cell surface expression of chemokine receptor cxcr4.Clinical & experimental metastasis · 2022Article
- The Role of PIM Kinases in Pediatric Solid Tumors.Cancers · 2022Review
- Chemical Composition and Immunomodulatory Activity of Essential Oils fromMolecules (Basel, Switzerland) · 2021Article
- Targeting PIM1-Mediated Metabolism in Myeloid Suppressor Cells to Treat Cancer.Cancer immunology research · 2021Article
- Chemical Composition and Immunomodulatory Activity ofBiomolecules · 2020Article
- Platelet-derived growth factor-BB promotes proliferation and migration of retinal microvascular pericytes by up-regulating the expression of C-X-C chemokine receptor types 4.Experimental and therapeutic medicine · 2019Article
- Molecular Players in Hematologic Tumor Cell Trafficking.Frontiers in immunology · 2019Review
- CXCR4- and BCR-triggered integrin activation in B-cell chronic lymphocytic leukemia cells depends on JAK2-activated Bruton's tyrosine kinase.Oncotarget · 2018Article
- Microenvironment-induced PIM kinases promote CXCR4-triggered mTOR pathway required for chronic lymphocytic leukaemia cell migration.Journal of cellular and molecular medicine · 2018Article
- Creating artificial lymphoid tissues to study immunity and hematological malignancies.Current opinion in hematology · 2017Review
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lymph node microenvironment provides chronic lymphocytic leukaemia (CLL) cells with signals promoting their survival and granting resistance to chemotherapeutics. CLL cells overexpress PIM kinases, which regulate apoptosis, cell cycle and migration. We demonstrate that BCR crosslinking, CD40 stimulation, and coculture with stromal cells increases PIMs expression in CLL cells, indicating microenvironment-dependent PIMs regulation. PIM1 and PIM2 expression at diagnosis was higher in patients with advanced disease (Binet C vs. Binet A/B) and in those, who progressed after first-line treatment. In primary CLL cells, inhibition of PIM kinases with a pan-PIM inhibitor, SEL24-B489, decreased PIM-specific substrate phosphorylation and induced dose-dependent apoptosis in leukaemic, but not in normal B cells. Cytotoxicity of SEL24-B489 was similar in TP53-mutant and TP53 wild-type cells. Finally, inhibition of PIM kinases decreased CXCR4-mediated cell chemotaxis in two related mechanisms-by decreasing CXCR4 phosphorylation and surface expression, and by limiting CXCR4-triggered mTOR pathway activity. Importantly, PIM and mTOR inhibitors similarly impaired migration, indicating that CXCL12-triggered mTOR is required for CLL cell chemotaxis. Given the microenvironment-modulated PIM expression, their pro-survival function and a role of PIMs in CXCR4-induced migration, inhibition of these kinases might override microenvironmental protection and be an attractive therapeutic strategy in this disease.
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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.