Finding out what kick starts infant leukaemia
There is growing evidence that many childhood leukaemias start to develop in foetal life. Immature blood cells in the foetus, called progenitor cells, may develop abnormalities that make them more susceptible to events after birth that transform them into rapidly proliferating leukaemic cells. This secondary event or ‘second hit’ required to develop leukaemia may happen several months/even years after birth. Some leukaemias that develop very early (<12months of age), often without a ‘second hit’; are called infant leukaemia and these children tend to do poorly even with intensive treatment.
I would like to investigate the foetal cells that undergo the ‘first hit’, in other words try to find the unique foetal progenitor cell that undergoes leukaemic transformation after birth. To do this I shall examine progenitor cells from foetal bone marrow samples (foetal tissue is obtained after specific written informed consent) and compare their characteristics and function with that of infant leukaemia cells. Foetal progenitor cells will also be modified by inducing the ‘first hit’ to see if that is sufficient for leukaemic transformation. This will help us identify unique preleukaemic foetal cells that initiate the development of infant leukaemia and ultimately design novel therapies to treat this refractory leukaemia.