Professor Tariq Enver, UCL Cancer Institute & Professor Shai Izraeli, Sheba Medical Center, Israel
Cure rates for B cell acute lymphoblastic leukaemia have increased over the past few decades but a large minority of children still die from their disease and those who survive may be left with long-term side effects. This project will take forward our understanding of the complex genetic changes underlying this disease, with the hope that this will lead to the development of new drugs that may successfully treat patients but with reduced side effects.
Amount of grant: £250,000 | Date of award: June 2014
B cell acute lymphoblastic leukaemia (B-ALL) is one of the most common cancers of childhood. Although cure rates are steadily improving, a large minority of children will die from their disease and in those who survive, side effects can be very severe due to the intensity of treatment.
It has been demonstrated that the first stages of childhood B-ALL start before a baby is born and that the disease progresses following the accumulation of serial genetic mutations in certain cells in the bone marrow. However it is still not clearly understood how normal human bone marrow makes B cells, which type of developing B cell is prone to becoming leukaemic, and why only a small percentage of children who are born with the early stages of leukaemia ultimately develop the disease.
In this project, the team will try to address these issues by studying B cells that have been produced in the laboratory from human stem cells. They will study a type of B cell leukaemia that occurs in children with Down syndrome (DS). Children with DS have a 33-fold increased risk of developing ALL and do not respond well to standard therapy. The team has recently discovered several genetic mutations occurring in DS leukaemias and will study the origins of leukaemia by introducing these genetic abnormalities into stem cells and very early blood cells. This will provide a unique model of leukaemia that will show how normal blood cells become leukaemic. It could also serve as an experimental model to test new drugs – for both DS leukaemia and other forms of the disease.
About the research team
This project is a collaboration between laboratories in the UK and Israel, representing two of the world’s leading authorities on leukaemia.
The Enver and Izraeli laboratories share a common interest in childhood ALL albeit from different perspectives. Professor Shai Izraeli is an expert on DS leukaemia; Professor Tariq Enver is a stem cell biologist, responsible for first identifying leukaemic stem cells in childhood B cell ALL.
Their complementary expertise will enable them to successfully carry out this ambitious project.
What difference will this project make?
The overarching goal of both teams is to identify new drugs to improve survival, with fewer side effects.
Read more: Acute lymphoblastic leukaemia