Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Alex Thompson, University of Nottingham
Award: £248,298.61
Awarded July 2023
Although childhood cancer treatments have improved in the last 10 years, many are still very toxic for children. Some current drugs can leave patients with long-term complications, including leukaemia late in life. Thankfully, this happens in only one in 100 patients but only around 10% of these children will survive for 5 years if they are unable to receive a bone marrow transplant.
A complete understanding of this ’secondary’ leukaemia in children is lacking. We urgently need effective and non-toxic drugs to treat secondary leukaemia, improve patient survival and quality of life.
Researchers believe that treatments that kill cancer cells by damaging their DNA could be linked to secondary leukaemia. If this DNA damage also affects a normal developing blood cell, then it increases the risk of that cell becoming cancerous.
Blood formation starts in the developing embryo and, through studying twins, researchers have traced the first signs of some infant and childhood leukaemias to the womb. To find kinder childhood leukaemia drugs, we need to identify what genetic changes occur at the earliest stages of blood cell development that allows leukaemia to ‘seed’ and grow alongside normal cells. This would help us find a way to target these leukaemic ‘seeds’ while keeping normal cells healthy.
In this project, Dr Alex Thompson at the University of Nottingham aims to compare the leukaemic seeds that initiate secondary leukaemia to healthy stem cells from the same patient. This will allow his team to find out what changes happen in the early stages of this type of leukaemia and look at which known or experimental drugs could target leukaemic ‘seeds’ without harming normal stem cells.
The researchers aim to identify exactly where DNA damage occurs in children with secondary leukaemia. Blood cells collected before, during and after children’s cancer treatments for secondary leukaemia will be examined for leukaemia-causing genetic mutations. Not all the blood cells will be leukaemic but, where leukaemia is detected, the researchers will convert the cells into embryo-like models in the laboratory. This will allow them to examine normal blood cell and leukaemia cell development from the same patient.
These groups of developing normal and leukaemia cells can then be used to study the effects of new treatments. The treatments will be based on the specific areas of DNA damage identified in the first objective and will be effective against the leukaemia ’seeds’ but not harmful to normal developing blood cells.
In this way, Dr Thompson hopes to provide evidence for effective and non-harmful drugs to accelerate them into clinical trials.