Dr Giulia Orlando, University of Oxford, is looking at the changes that happen to gene activity in juvenile myelomonocytic leukaemia (JMML). By identifying new treatment targets, her research could help more children survive JMML.

The challenge

Juvenile myelomonocytic leukaemia (JMML) is a rare form of cancer affecting children. There are very few effective treatments for this cancer, and the only chance of a cure is a bone marrow transplant. But even with a transplant, 35% of children see their cancer come back.

In about nine in ten children, their JMML cells carry mutations in the DNA which activate a mechanism inside cells called the RAS pathway. But even though we’ve known about this vulnerability for the last 30 years, scientists have not yet been able to develop a targeted treatment for JMML.

We need to find new vulnerabilities in JMML, which could lead us to treatments that can improve children’s chances of survival.

The science behind the research

To find new effective treatments for JMML, Dr Giulia Orlando is looking for potential drug ‘targets’ – proteins inside cells which when blocked could kill JMML cells or stop them growing.

The mutations which activate the RAS pathway that often occur in JMML lead to changes in the activity of many genes. In her John Goldman Fellowship, Giulia will be investigating exactly how activation in the RAS pathway leads to these changes in gene activity. In doing this, she hopes to find potential vulnerabilities that can be exploited.