The purpose of this project is to create an in vitro model of disease for a childhood leukaemia which is caused by a harmful mutation resulting in an abormal fusion of two genes. These genes play an important role in normal blood development, however when fused together, they create an oncogene which impedes haematopoiesis. This fusion oncogene 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 as a platform from which we can study early leukaemic development, as well as screen new therapeutic drugs which will target the fusion oncogene without damaging healthy blood cells.
This research will allow us to further our understanding of fusion oncogene leukaemias and how they cause disease. 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. 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.
We have successfully created a model of disease recapitulating the development of normal blood cells. We can then turn on our fusion oncogene and track the phenotypic and characteristic leukaemic changes happening to the blood cells.
We have used pluripotent stem cells and created organoid bodies which have the ability to generate and shed blood cells in culture. Note the budding red-, green- and yellow-cells from the three organoid bodies in close proximity. These are island of haemogenic endothelium which will transition and turn into blood cells floating in the medium. The red-cells are haemogenic endothelium from wich the green-blood cells emerge from. We can see the transition from haemogenic endothelium into blood cell in the areas are appear as yellow.
Katerina Terolli, Ritika Saxena and Dr Floyd Hassenrüeck from Prof Andrew Elefanty’s Blood Development Laboratory.