Many childhood leukaemias start to develop before birth due to accumulation of mutations during foetal development. It’s well known that having the wrong number of chromosomes is often linked to leukemia. Children with Down's Syndrome have an extra copy of chromosome 21 in their cells and are 500 times more likely than other children of developing leukemia. However, there’s still a lot we don’t understand about how blood cells in foetuses develop, how they change over time, and how these changes lead to leukaemia.
Two key questions will be answered by this proposed research:
1. How does having an extra chromosome (aneuploidy) interfere with the development of blood cells in the foetus?
2. How does it affect the way mutations build up in blood stem cells, and how do these mutations contribute to leukaemia?
To answer these questions, we will be taking a following approach:
1. We will analyze the foetal liver and bone marrow from children with Down’s Syndrome using advanced techniques that allow us to study individual cells. This will provide a detailed picture of how growth of blood cells might be disrupted.
2. We will use powerful whole genome sequencing to catalog all the genetic mutations that occur in the blood stem cells of foetuses with Down’s Syndrome. This will allow us to understand how these muataions might contribute to the development of leukemia.
Importantly, by looking at both the internal factors (like genetic mutations) and the external factors (like how the cells develop in the body) that affect blood cell growth, we will uncover how having an extra chromosome triggers or accelerates the development of leukemia. Ultimately, this research could give us a much better understanding of the early steps that lead to leukemia, not just in children with Down’s Syndrome, but in general. By identifying these early events, we could potentially develop better ways to diagnose, monitor, and treat this devastating disease in the future.
