The choroid plexus stroma constitutes a sanctuary for paediatric B‐cell precursor acute lymphoblastic leukaemia in the central nervous system

摘要: 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 specific cellular microenvironments which can promote survival, quiescence, and therefore chemoresistance leukaemia cells in system. Herein, we showed by immunofluorescence electron microscopy that xenotransplanted mice, leukaemic infiltrate connective tissue stroma choroid plexus, brain structure responsible production cerebrospinal fluid. The ultrastructural also are able to migrate through blood vessels located plexus stroma. In short-term co-cultures, established strong interactions with human fibroblasts, mediated an increased expression ITGA4 (VLA-4)/ITGAL (LFA-1) their ligands VCAM1/ICAM1. Upon contact cells, fibroblasts acquired cancer-associated fibroblast phenotype, α-SMA vimentin as well pro-inflammatory factors. Human capacity reduce proliferative index blasts survival methotrexate cytarabine. inhibition VLA-4/VCAM-1 using anti-VLA-4 antibodies, blockade Notch signalling pathway γ-secretase inhibitor partially restored chemotherapy sensitivity cells. We propose constitutes sanctuary © 2020 Authors. Journal Pathology published John Wiley & Sons, Ltd. on behalf Pathological Society Great Britain Ireland.