The purpose of this project is to create an in vitro model of a type of childhood leukamia which is caused by a two genes fusing together and creating a harmful mutation. These genes individually play an important role in normal blood development, however when fused together, they create a mutation which impedes normal blood formation. This fusion mutation is one of the leading drivers of infant acute myeloid leukaemia. This model of disease will allow us to compare the development of healthy blood cells to the development of diseased blood cells in the presence of these fusion mutations. This model will be used a platform from which we can study early leukemic development as well as screen new therapeutic drugs which will target the fusion mutation without damaging healthy blood cells.
Impact
This research will allow us to further our understanding of blood development and how fusion mutations cause disease such as leukaemia. We have the potential to discover new and effective treatments for children battling this form of blood cancer and therefore significantly increasing the survival rates for these children. Furthermore, there would be significant benefits to the healthcare system worldwide through the reduction of ongoing health costs associated with blood cancers and their complications. Overall, this will help improve health care, patient care and wellbeing.
reNEW research
We have successfully created a model which recapitulates the development of normal, healthy blood cells. Using this model we can successfully turn on our fusion mutation of interest and observe normal blood cells turn into keukaemic cells in a dish.
Image description
Here we have an image of pluripotent stem cells which have come together to create an organoid bodie. These organoid bodies are self-organised three dimensional structures which recapitulate the function of various complex systems. In our lab we use these organoid bodies them to specifically study human blood development and blood disease.
The red cells clustered on the outside and in the middle of this organoid body represent a population known as haemogenic endothelium which is what gives rise to blood cells.
Once the blood cells are released in our culture we can collect them and turn on our fusion mutations to study leakaemic transformation of these cells.
Credits
Katerina Terolli from Dr Andrew Elefanty’s Blood Development lab, MCRI.
