How does T-cell acute lymphoblastic leukaemia go to the brain?

Acute lymphoblastic leukaemia (ALL) is the commonest cancer in children. There are two types – B-cell(B-ALL) and T-cell (T-ALL).

T-ALL is rarer than B-ALL and harder to treat. If T-ALL reoccurs (relapses) only two-three out of ten children will be cured. Leukaemia is a blood cancer, but it also travels elsewhere in the body.

This project investigates leukaemia that has spread to the brain. This is common in T-ALL. Studying T-ALL in the brain is very important because:

1. The brain is a common place for leukaemia to reoccur after treatment
2. All children are given treatment (chemotherapy or radiotherapy) to try and prevent the leukaemia reoccurring. These treatments are harsh and can cause long-term damage.
3. There are no good treatments if T-ALL reoccurs.

In this project we will find out which genes are needed for T-ALL survival in the brain by:

1. Using a state-of-the-art technology called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). In nature CRISPR is used by bacteria to attack and remove genes from infecting viruses. This is called “gene-editing”. Scientists have adapted this natural process to remove genes in human cells. Using T-ALL cells grown in the laboratory, we will use CRISPR to make a collection of T-ALL cells, each with a different gene removed. We will inject the cells into mice to see which genes are needed for brain leukaemia to develop.
2. Measuring which genes are active in T-ALL cells from the brains of mice to identify the genes T-ALL needs to “switch-on” when it gets to the brain.
3. We will then test whether blocking these key genes, using drugs or chemicals, will kill T-ALL cells and prevent brain leukaemia in mice.

Together these experiments will improve our scientific knowledge and help develop new treatments for brain leukaemia.