Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Dr Anindita Roy, University of Oxford
Award: £219,194.66
Awarded December 2020
Although it is possible to cure 90% of children with the commonest type of blood cancer (leukaemia), unfortunately only 50% of children who develop leukaemia before their first birthday can be cured.
These infant leukaemias are usually associated with a gene called MLL, and a better understanding of these treatment resistant leukaemias is required.
We have developed a model of infant leukaemia by creating an MLL leukaemia gene in normal cells so that those cells behave just like infant leukaemia. We now want to use this model to understand the pathways that drive this aggressive disease and test new drugs for treatment.
Previous research in our lab has shown that in some cases, MLL leukaemia depends on abnormal production of a protein called CD133. The gene that makes CD133 is turned on by mistake, and as a result it appears on the surface of leukaemia cells.
In this project, we want to use leukaemia cells from the model we have developed, and from patients to understand how CD133 contributes to their ability to resist treatment. To do this we will analyse how CD133 is regulated in normal cells as well as leukaemic cells, and whether suppressing its activity can make the leukaemia less aggressive.
The results of these experiments will inform us whether we can use CD133 to develop novel effective treatments, particularly by targeting it as a ‘label’ unique to treatment-resistant infant leukaemia cells. In order to do this we will develop a new type of immune treatment called “CAR-iNKTcells” designed to recognise the leukaemia cells marked with CD133 and destroy them. This project will help identify how CD133 contributes to the aggressive nature of infant leukaemia.
It can then be exploited to design novel therapies for leukaemia and potentially also for other childhood cancers that express CD133.