How do leukaemia stem cells talk to the immune system in juvenile myelomonocytic leukaemia?

Juvenile myelomonocytic leukaemia (JMML) is an extremely rare and aggressive form of leukaemia - only around 10 children are diagnosed in the UK per year. There are no effective current treatment options. Haematopoietic stem cell transplantation (HSCT) is the only chance of curing JMML, but there are many side effects and the cancer comes back in four in 10 children. At this point, the cancer is incurable. The unique nature of the disease and small number of cases means that there is little research into better treatment options.

In 2015, Professor Adam Mead’s team at the University of Oxford found that there were specific cells which caused JMML to come back after treatment - JMML leukaemia stem cells. Based on this finding, the team found a protein, called CD96, that is only found on the surface of these cells. This work is still in progress, but could lead to the first immunotherapy for JMML.  It could also form part of a test that could tell doctors whether a child is relapsing, before any symptoms are present. This could allow earlier treatment and give the best chance of survival.

In this project, the research team hope to find a new way to target JMML cells that could be used as a treatment alongside the planned immunotherapy, which would improve survival. They will be investigating how JMML leukaemic stem cells make the cancer come back after treatment.

The researchers believe that the stem cells have the ability to switch off the immune system, which should be hunting down any JMML cells that are left over after HSCT. If the immune system is switched off, it could leave JMML cells alive, leading to relapse. The team plan to study how the stem cells interact with the immune system at all times from diagnosis to relapse. Professor Adam Mead hopes that the study of these interactions will help to understand the mechanisms that make JMML resistant to treatment and suggest new ways to treat it.