ArticleCellular oncology (Dordrecht, Netherlands)2025
Meningeal leukaemic aggregates as foci of cell expansion and chemoresistance in acute lymphoblastic leukaemia metastasis.
Article in Cellular oncology (Dordrecht, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeCentral nervous system (CNS) involvement and/or relapse remains one of the most important causes of morbidity/mortality in paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients. To identify novel therapeutic targets and develop less aggressive therapies, a better understanding of the cellular and molecular microenvironment in leptomeningeal metastases is key. Here, we aimed to investigate the formation of metastatic leptomeningeal aggregates and their relevance to the expansion, survival and chemoresistance acquisition of leukaemia cells.
methodsWe used BCP-ALL xenograft mouse models, combined with immunohistofluorescence and flow cytometry, to study the development of CNS metastasis and the contribution of leptomeningeal cells to the organisation of leukaemic aggregates. To in vitro mimic the CNS metastasis, we established co-cultures of three-dimensional (3D) ALL cell spheroids and human leptomeningeal cells (hLMCs) and studied the effects on gene expression, proliferation, cytokine production, and chemoresistance.
resultsIn xenografted mice, ALL cells infiltrated the CNS at an early stage and, after crossing an ER-TR7
conclusionOur results provide evidence for the formation of metastatic ALL-leptomeningeal cell aggregates, their pro-inflammatory profile and their contribution to leukaemic cell expansion, survival and chemoresistance in the CNS.
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