05 October 2020

Scientists have found that a specific area of the central nervous system (CNS), the choroid plexus, could help childhood acute lymphoblastic leukaemia cells resist treatment.

The choroid plexus is where cerebrospinal fluid is produced in the ventricles of the brain. Drs Alberto Varas and Ángeles Vicente and colleagues at Complutense University in Madrid say their work shows the choroid plexus serves as a “sanctuary” for tumour cells, allowing them to elude chemotherapy and potentially enabling CNS relapse.

Despite current CNS-directed therapies for childhood B-cell precursor acute lymphoblastic leukaemia, “relapse at this anatomical site still remains a challenging issue”, the researchers write in the Journal of Pathology.

The team set out to study this cellular microenvironment in mice, using a range of techniques including electron microscopy. They showed that leukaemia cells can infiltrate the connective tissue stroma of the choroid plexus.

Tests showed that these leukaemia cells attach strongly to stroma cells, changing them into a cancer-supporting phenotype that protects the leukaemia cells against chemotherapy, and triggers inflammation.

However, the sensitivity to chemotherapy could be partially restored with the use of antibodies that block VLA-4 or by a drug which blocks the Notch signalling pathway.

The authors write: “We propose that the choroid plexus stroma constitutes a sanctuary for B-cell precursor acute lymphoblastic leukaemia cells in the central nervous system.”

Dr Vicente said: “The fact that relapses continued to occur in the central nervous system despite prophylactic treatment led us to suspect that some cells might remain hidden in small, practically undetectable groups elsewhere.”

Dr Lidia Fernández-Sevilla, first author of the study, added: “Studies like ours could be essential to design more effective therapeutic strategies in the future aimed at preventing tumour cells from colonising niches in the central nervous system or eliminating the cells that have already established themselves in these sites.”

Source: Fernández-Sevilla LM, Valencia J, Flores-Villalobos MA, Gonzalez-Murillo Á, Sacedón R, Jiménez E, Ramírez M, Varas A, Vicente Á. (2020) “The choroid plexus stroma constitutes a sanctuary for paediatric B-cell precursor acute lymphoblastic leukaemia in the central nervous system.” J Pathol, doi: 10.1002/path.5510