Identifying the genetic changes in T-cell acute lymphoblastic leukaemia that fails to respond to chemotherapy

Acute lymphoblastic leukaemia (ALL) is the commonest childhood cancer, occurring in approximately 400 children each year in the UK. Although many children can be cured, a significant number still die from the disease. Recent work has focused on trying to identify which children have leukaemia that can be cured easily with current chemotherapy and which children have leukaemia which is much harder to treat and will therefore need stronger chemotherapy or new types of treatment. This work has shown that children with leukaemia that fails to respond to the first four weeks of treatment, called ‘primary refractory’ leukaemia, have a very poor outcome. Importantly, primary refractory leukaemia occurs more commonly ina subtype of ALL called T-ALL, occurring in 10% of T-ALL cases. However, at present, we do not know why these children have such aggressive disease and, unfortunately, we do not have any available therapy for many of these patients.

Cancer is a genetic disease, which means that it occurs due to changes in the genetic code of the cell, which is contained in the cell’s genes. Whilst it is well known that ALL occurs due to mutations in the genes in an immature blood cell, we do not know the exact changes that occur in primary refractory T-ALL. This project therefore aims to perform detailed analyses on leukaemia bone marrow samples collected from patients with primary refractory T-ALL. We will use state of the art sequencing techniques which allow us to read the DNA blueprint of each tumour to identify the genetic changes that cause this type of leukaemia. Further work will look at how these changes affect blood cells and it is hoped that this greater understanding will lead to the development of new treatments to target this disease and improve patients’ outcomes.