Acute myeloid leukaemia (AML) is the second most common form of childhood leukaemia. It has a substantially worse outlook than the more common form, acute lymphoblastic leukaemia (ALL).
It is now well known that errors (mutations) in our blood stem cells lead to the development of AML. A large amount of research has been carried out to identify the mutations that result in leukaemia and more than 250 mutations have been identified.
We know that a single mutation is not enough to cause leukaemia; each child with AML will have between 5 and 20 of these mutations. However it is thought that one mutation can act as a master “trigger”. This is termed the “driver” mutation.
In most cases we don’t really know the role played by other mutations that are present in leukaemia cells. The idea behind this project is that a “driver” mutation needs a “secondary driver” to convert a normal cell into a leukaemia cell and these “secondary drivers” are among the other mutations that we know are present.
Although most childhood leukaemias are sporadic, there are familial syndromes where children can inherit a genetic mutation that leads to the development of AML. Although rare, these familial cases provide an important opportunity for the study of the genetics of AML because the “driver” mutation is already known.
In this project, Dr Payne and colleagues aim to create a system where they can test the roles of possible secondary drivers to see which are the most important in the development of leukaemia.
The model system uses a small freshwater fish called the zebrafish. Zebrafish develop leukaemia in the same way as humans and the genes that are responsible for programming blood development are the same. Zebrafish offer an excellent system in which to study blood and leukaemia because the young are completely transparent, enabling blood development to be seen in real time under a microscope