Using genetics to understand why acute myeloid leukaemia cells don’t respond to treatment

Childhood acute myeloid leukaemia (AML) is an aggressive disease which leads to around four in ten children dying. This can be because the treatment didn’t have enough of an effect, because the treatment was too toxic, or because the leukaemia came back after treatment. There are not many treatments for these children, and we don’t know much about leukaemia cells that resist or do not respond to treatment. These cells are called leukaemia stem cells and can still be in the patient after treatment, leading to terminal disease.  

In a current UK clinical trial for children with AML, bone marrow samples are being taken to track the leukaemia stem cells in patients. The research team at the University of Glasgow, led by Dr Karen Keeshan, will use the samples collected in the trial and look at what genes are inside each individual leukaemia stem cell that doesn’t respond to treatment. The researchers think that how the leukaemia stem cells look changes as the disease progresses in the patient. To test this, they will use very sensitive single cell technology to look at the genetics of the leukaemia stem cells at three different stages of the disease: at diagnosis, following treatment, and when the patient relapses. They will then find which cells did not respond to treatment and use drug databases to pick drugs that will kill these cells, based on their different genetics.

Identifying the leukaemia stem cells that do not die with treatment will help design more precise treatment options for the patient. Dr Karen Keeshan hopes to provide treatment strategies for children with even the most aggressive disease, which will save lives.