Investigating the Role of Choroid Plexus Endothelial Cells in Central Nervous System Leukaemia

Leukaemia comprises a group of cancers originating in blood and bone marrow, with B-cell acute lymphoblastic leukaemia (B-ALL) being notably aggressive. Despite prophylactic treatments aimed at preventing central nervous system infiltration, leukaemia cells often migrate to the brain and establish sanctuary sites within the choroid plexus. The choroid plexus, responsible for producing cerebrospinal fluid, harbours multiple cell types, including endothelial cells that have been implicated in promoting cancer cell survival. However, the precise molecular and cellular mechanisms of these interactions remain poorly understood. This thesis investigates how endothelial cells in the choroid plexus support the survival of NALM6 B-ALL cells. Single-cell RNA sequencing data from the cerebrospinal fluid of patients diagnosed with leukaemia will be examined to identify upregulated genes and pathways when compared to healthy choroid plexus cell datasets. Interactome analysis will be used to model potential cross-talk between cancer and stromal cells, highlighting possible targets that underpin the ability of B-ALL cells to evade therapeutic interventions. Additionally, a cell-line co-culture and trans well assay will be employed to visualise the spatial distribution and movement of leukaemia cells, using immunostaining assays to confirm the involvement of specific cell types and pathways. Findings indicate that the VEGF signalling pathway may play a pivotal role in mediating interactions between endothelial cells and B-ALL cells within this microenvironment. By focusing on the pathways that support leukaemia cell survival in the choroid plexus, this research seeks to advance current understanding and inform future interventions designed to enhance understanding of leukaemia invasion of the human CNS.