What is this research looking at?

T cells are type of white blood cell that helps us fight infections. When T cells acquire mutations in specific genes (or segments of DNA) they can grow out of control leading to T cell acute lymphoblastic leukaemia (T-ALL). During normal development of T cells, many genes switch on and off to help T cells mature. In T-ALL some of these genes get stuck in an ‘on-state’ through acquired mutations. With our collaborators, we wrote a computer program that analysed the genomes of many different T-ALLs to identify a number of genes that are stuck in the ‘on-state’. One of these genes is called FAT1 and it is overexpressed (switched on) in 50% of patients with T-ALL.

Through my research I aim to determine if FAT1 overexpression is required for the survival of leukaemic cells. I will also use sequencing techniques to identify new mutations that initiate expression of FAT1 in T-ALL. Importantly, FAT1 makes a transmembrane protein (a molecule that sticks out of cells) which can be recognised by therapeutic antibodies. If I successfully demonstrate that FAT1 is indeed a vulnerability in T-ALL it may provide a new avenue to treat this leukaemia.

What could this mean for people affected by leukaemia?

It is incredibly important that we continue to identify new targets for therapies in leukaemia. This helps to design safer and more personalised treatments with the hope of fewer side effects. My project has identified a promising target called FAT1 in T cell acute lymphoblastic leukaemia. If I am successful in showing FAT1 is critical for leukaemia growth or maintenance, we may be able target it with the latest technologies including therapeutic antibodies or chimeric antigen receptor T cell (CAR-T) therapy.

Leukaemia UK funding has provided a fantastic opportunity to work on a project that has great promise for those with T cell acute lymphoblastic leukaemia and potentially other leukaemias too.

Sunniyat Rahman

Official title of project: Characterisation of an aberrantly expressed protocadherin FAT1 isoform in T cell acute lymphoblastic leukaemia