Targeting the genes that cause AML
Acute myeloid leukaemia is a blood cancer affecting ~3000 people each year in the UK. Chemotherapy cures 30-40% of younger patients, but less than 10% of older patients survive five years from diagnosis. To develop improved treatments we need to better understand what makes a healthy blood cell become a leukaemic cell. We know that damage to the genetic code carried by all blood cells (mutations) is important. However, we don't fully understand what these mutations do to healthy cells, and how mutations in different genes work together to cause leukaemia. One in five AML patients has a mutation in genes called isocitrate dehydrogenase 1 (IDH1) or IDH2. These leukaemias make an abnormal chemical called 2-hydroxyglutarate, which we think impairs how the body 'reads' other genes that control development of blood cells. I have discovered that many AML patients with IDH mutations also have mutations in SRSF2, a gene important in processing the gene message, something called RNA. The proposed experiments will help us understand how these mutations work together. They will also profile and evaluate new candidate drugs which target the mutated form of IDH1 to see whether these successfully kill leukaemia cells, potentially leading on to clinical trials.