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Few reports have addressed the study of the specific cellular microenvironments which can promote the survival, quiescence, and therefore chemoresistance of B\u2010cell 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\u2010term co\u2010cultures, leukaemic cells established strong interactions with human choroid plexus fibroblasts, mediated by an increased expression of <jats:italic>ITGA4<\/jats:italic> (VLA\u20104)<jats:italic>\/ITGAL<\/jats:italic> (LFA\u20101) and their ligands <jats:italic>VCAM1\/ICAM1<\/jats:italic>. Upon contact with leukaemia cells, human choroid plexus fibroblasts acquired a cancer\u2010associated fibroblast phenotype, with an increased expression of \u03b1\u2010SMA and vimentin as well as pro\u2010inflammatory 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\u20104\/VCAM\u20101 interactions using anti\u2010VLA\u20104 antibodies, and the blockade of Notch signalling pathway by using a \u03b3\u2010secretase inhibitor partially restored chemotherapy sensitivity of leukaemia cells. We propose that the choroid plexus stroma constitutes a sanctuary for B\u2010cell precursor acute lymphoblastic leukaemia cells in the central nervous system. \u00a9 2020 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5510","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T01:59:56Z","timestamp":1595210396000},"page":"189-200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The choroid plexus stroma constitutes a sanctuary for paediatric <scp>B<\/scp>\u2010cell precursor acute lymphoblastic leukaemia in the central nervous system"],"prefix":"10.1002","volume":"252","author":[{"given":"Lidia M","family":"Fern\u00e1ndez\u2010Sevilla","sequence":"first","affiliation":[{"name":"Department of Cell Biology, School of Medicine 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