ArticleThe Journal of pathology2020
The choroid plexus stroma constitutes a sanctuary for paediatric B-cell precursor acute lymphoblastic leukaemia in the central nervous system.
Article in The Journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Central nervous system involvement in acute lymphoblastic leukemia: pathogenesis and targeted therapy.Leukemia · 2026Review
- Acute anti-obesity treatment with celastrol reduces body weight, cerebral inflammation and metabolic imbalances in mice.Molecular medicine (Cambridge, Mass.) · 2026Article
- Assessing changes in brain structure in new-onset children with acute lymphoblastic leukemia.Pediatric research · 2025Article
- Meningeal leukaemic aggregates as foci of cell expansion and chemoresistance in acute lymphoblastic leukaemia metastasis.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure.HemaSphere · 2025Article
- Cancer associated fibroblasts in tumors: focusing on solid tumors and hematological malignancies.Frontiers in oncology · 2025Review
- Molecular and cellular mechanisms of chemoresistance in paediatric pre-B cell acute lymphoblastic leukaemia.Cancer metastasis reviews · 2024Review
- The path to leptomeningeal metastasis.Nature reviews. Cancer · 2024Review
- Review
- Systematic Analysis of the Prognostic Significance and Roles of the Integrin Alpha Family in Non-Small Cell Lung Cancers.Advances in therapy · 2023Article
- Integrins and the Metastasis-like Dissemination of Acute Lymphoblastic Leukemia to the Central Nervous System.Cancers · 2023Review
- 25-Year Storage of Human Choroid Plexus in Methyl Salicylate Preserves Its Antigen Immunoreactivity.Turk patoloji dergisi · 2023Article
- Recent advances in drug delivery and targeting to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Acute lymphoblastic leukemia cells are able to infiltrate the brain subventricular zone stem cell niche and impair neurogenesis.Haematologica · 2022Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Infant leukaemia - faithful models, cell of origin and the niche.Disease models & mechanisms · 2021Review
- Metabolic Reprogramming and Cell Adhesion in Acute Leukemia Adaptation to the CNS Niche.Frontiers in cell and developmental biology · 2021Review
- The Impact of Small Extracellular Vesicles on Lymphoblast Trafficking across the Blood-Cerebrospinal Fluid Barrier In Vitro.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite current central nervous system-directed therapies for childhood B-cell precursor acute lymphoblastic leukaemia, relapse at this anatomical site still remains a challenging issue. Few reports have addressed the study of the specific cellular microenvironments which can promote the survival, quiescence, and therefore chemoresistance of B-cell precursor acute lymphoblastic leukaemia cells in the central nervous system. Herein, we showed by immunofluorescence and electron microscopy that in xenotransplanted mice, leukaemic cells infiltrate the connective tissue stroma of the choroid plexus, the brain structure responsible for the production of cerebrospinal fluid. The ultrastructural study also showed that leukaemia cells are able to migrate through blood vessels located in the choroid plexus stroma. In short-term co-cultures, leukaemic cells established strong interactions with human choroid plexus fibroblasts, mediated by an increased expression of ITGA4 (VLA-4)/ITGAL (LFA-1) and their ligands VCAM1/ICAM1. Upon contact with leukaemia cells, human choroid plexus fibroblasts acquired a cancer-associated fibroblast phenotype, with an increased expression of α-SMA and vimentin as well as pro-inflammatory factors. Human choroid plexus fibroblasts also have the capacity to reduce the proliferative index of leukaemic blasts and promote their survival and chemoresistance to methotrexate and cytarabine. The inhibition of VLA-4/VCAM-1 interactions using anti-VLA-4 antibodies, and the blockade of Notch signalling pathway by using a γ-secretase inhibitor partially restored chemotherapy sensitivity of leukaemia cells. We propose that the choroid plexus stroma constitutes a sanctuary for B-cell precursor acute lymphoblastic leukaemia cells in the central nervous system. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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