Located in an area of ​​the brain where tumors hide from chemotherapy

Although survival in childhood acute lymphoblastic leukemia has increased greatly in recent years, 20% of cases still cannot be cured, mainly because the tumor cells avoid chemotherapy by hiding in the nervous system. Now, a study by the Complutense University has discovered what place that is.

The Niño Jesús hospital in Madrid and the Autonomous University of Chihuahua (Mexico) also participated in the research, published in 'The Journal of Pathology'. Researchers have discovered that the stroma of the choroid plexus, located in the Central Nervous System (CNS), acts as a hiding place for tumor cells, allowing them to escape chemotherapy and potentially causing subsequent relapses in childhood acute lymphoblastic leukemia.

The choroid plexus is a structure located in the cerebral ventricles and is responsible for the production of cerebrospinal fluid. Leukemic cells, although they are mainly located in the bone marrow, are capable of spreading to other areas of the body, having a special desire to infiltrate the CNS, explains the UCM in a statement.

"The fact that relapses continued to occur in the CNS despite prophylactic treatment made us suspect that some cells could remain hidden in small groups, practically undetectable in other areas, and could be responsible for relapses after a while," explains Ángeles Vicente, researcher. from the UCM Faculty of Medicine.

To carry out the study, the researchers infused immunodeficient mice with leukemic cells from patients, analyzing, using immunofluorescence and electron microscopy techniques, the brain location of the metastatic tumor cells in the CNS and identifying the location in the choroid plexus.

This in vivo technique was combined with in vitro assays to study the cellular interactions established between leukemic cells and choroid plexus stromal cells and their effects on chemoresistance.

Around 15-20% of pediatric patients with acute lymphoblastic leukemia are not cured, with relapses in the CNS being the main cause of morbidity and mortality due to the disease in the pediatric population. "Work like this may be essential to design, in the future, more effective therapeutic strategies aimed at preventing the settlement of tumor cells in different niches of the CNS or eliminating cells that have already established themselves in these places," says Lidia Martínez, first author of the work.

"This would represent a great advance in the treatment of the disease, reducing these relapses and increasing, even more, the chances of cure," predicts the UCM researcher. Although the study is focused on childhood acute lymphoblastic leukemia, the researchers see it as feasible that the sanctuaries used by leukemic cells in children could be shared by adults, where CNS relapses account for 5%.