Most babies with acute lymphoblastic leukemia (ALL) have a particular fault in the DNA of their cancer cells, in the so-called MLL gene. Every year, five babies younger than one year old in the Netherlands are diagnosed with ALL, four of whom have this MLL change. Despite heavy treatment with chemotherapy, children with MLL leukemia have a poor chance of survival. New, better treatments are desperately needed.
More focused than ever
Dr. Ronald Stam, group leader at the Princess Máxima Center for pediatric oncology, carries out research into MLL leukemia in babies. He says: ‘MLL changes are relatively rare, but the survival of children with this gene fault is far behind that of other children with leukemia. Together with researchers in Italy, Spain and the United Kingdom, we are now joining forces to explore new, targeted therapies for babies with MLL leukemia more thoroughly and systematically than ever before.’
'The strength of this project lies in the combination of our expertise,' explains Stam. ‘One of the groups is very good at studying the genome – the entire DNA of the cancer. These colleagues will compare the tumor DNA of babies with MLL leukemia, with the aim of finding new targets for treatment. We then take over from them: my group specializes in linking possible targets for therapy to existing or new drugs.’
Suitable target
To find a good target for therapy, the Stam group will look for gene changes that are unique to the leukemia, but do not occur in healthy cells. That is a key feature of a candidate drug: it must work as effectively as possible, with as few side effects as possible. The Stam group will also study possible drugs in the lab to find out why they do or don’t work – in order to better understand if they will also have a chance of success in the clinic.
After looking at cells in the lab, the most promising candidate drugs will be studied in mice. This will help the researchers to find out whether the therapy also has the intended effect within the complexity of a whole body. With that aim, one of the research groups in the international consortium is contributing with a new mouse model in which they can mimic the development of MLL leukemia.
Risk of recurrence
In addition to the search for new drug targets, the team will focus on research to lower the risk of the cancer coming back after treatment. Ronald Stam: ‘Using single cell sequencing, a technology to analyze DNA at the level of individual cells, we have discovered an important group of cells: the more of these cells we see at diagnosis, the greater the chance that the cancer will come back. Unfortunately, that is the case in most children with MLL leukemia. In this project, we’re strongly committed to finding a way to switch off this group of cells.’
The international team’s research is supported by Fight Kids Cancer, a funding program of the European Science Foundation. Together they form a so-called biology consortium within Interfant, the group of collaborating experts that develops the treatment protocol for treating babies with leukemia all over the world. Ronald Stam: ‘That is a huge advantage for the research: thanks to this integration with healthcare, we will ultimately be able see whether our findings actually lead to an improved survival.’