An area of the brain where tumor cells shelter from chemotherapy in childhood leukaemia

September 25, 2020

The stroma of the choroid plexus is one of the locations within the central nervous system (CNS) that serves as a shelter for tumour cells, allowing them to elude chemotherapy and potentially cause subsequent relapses in childhood acute lymphoblastic leukaemia, according to research led by the Complutense University of Madrid (UCM).

The choroid plexus is a structure located in the ventricles of the brain and is responsible for the production of cerebrospinal fluid. Although leukaemia cells are primarily located in the bone marrow, they are also capable of spreading to other areas of the body and show a particular propensity to infiltrate the CNS.

"The fact that relapses continued to occur in the CNS despite prophylactic treatment led us to suspect that some cells might remain hidden in small, practically undetectable groups elsewhere, and could be responsible for subsequent relapses", explained Ángeles Vicente, a researcher in the Department of Cell Biology at the UCM School of Medicine.

Besides identifying the hiding place, the study published in the Journal of Pathology also reveals how leukaemia cells elude chemotherapy: by interacting with stroma cells in the choroid plexus, modifying the microenvironment to ensure their own survival.

The Niño Jesús Hospital in Madrid and the Autonomous University of Chihuahua (Mexico) were also involved in the research.

A breakthrough for more effective treatment

To carry out the study, the researchers infused leukaemic cells from patients into immunodeficient mice and then used immunofluorescence and electron microscopy to determine the cerebral location of metastatic tumour cells in the CNS, successfully identifying the site in the choroid plexus.

This in vivo technique was combined with in vitro assays to study the cell interactions that take place between leukaemia cells and choroid plexus stroma cells and their effects on chemoresistance.

About 15-20% of paediatric patients with acute lymphoblastic leukaemia are not cured, and relapses in the CNS are the main cause of morbidity and mortality from the disease in the paediatric population.

"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 CNS or eliminating the cells that have already established themselves in these sites. This would represent a breakthrough in treatment of the disease, reducing relapses and further increasing the chances of a cure", predicted Lidia Martínez Fernández de Sevilla, a postdoctoral researcher in the Department of Cell Biology and the first named author of the study.

The research focused on childhood acute lymphoblastic leukaemia because the group only works with paediatric samples, but experts believe it is feasible that leukaemia cells might use the same hiding places in adults --where 5% of relapses are related to the CNS-- as they do in children.
-end-
Reference: Lidia M. Fernández-Sevilla, Jaris Valencia, Miguel A. Flores-Villalobos, África González-Murillo, Rosa Sacedón, Eva Jiménez, Manuel Ramírez, Alberto Varas y Ángeles Vicente. "The choroid plexus stroma constitutes a sanctuary for paediatric B-cell precursor acute lymphoblastic leukaemia in the central nervous system". J Pathol 2020 Jul 19. doi: 10.1002/path.5510.

Universidad Complutense de Madrid

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.