Dr Gerstung leads a research group at the European Bioinfomatics Institute (EMBL-EBI), one of HDR UK’s research partners. His recent acute AML study found genetically modified precursor cells up to ten years prior to diagnosis. This indicates that, although AML usually manifests without prior symptoms, there is probably a slow disease evolution in many cases. This raises hopes for new avenues of early detection and prevention.
Dr Gerstung said: “It’s great that at HDR UK, we are facilitating access to existing cohorts across the UK and linking data between molecular characterisation and health datasets. Our study underscores the value of establishing research cohorts, providing samples, materials and data that can be tapped into by different researchers.”
Why research into AML is important
AML is a very aggressive form of leukaemia, which manifests suddenly and progresses rapidly, without obvious prior symptoms. Previous studies have recognised that leukaemic precursor cells are often present, which could have arisen a number of years prior to diagnosis.
“We observed that some cells carry mutations that are common in the process of normal ageing. We recognised that these mutated cells can share similarities with leukaemic cells and we could identify genetic patterns to discriminate the dangerous from the benign,” said Dr Gerstung.
This project would not be possible without collaboration. The team worked closely with partners at the Wellcome Sanger Institute where the genome sequencing was performed, and Dr Gerstung’s team analysed the outcomes.
They used the World Health Organisation’s EPIC cohort of 500,000 individuals from across Europe. These had been recruited more than 15 years ago to study their cancer risk, looking at determinants leading to cancer such as lifestyle choices, exposures and genetic factors.
As the cohort of healthy individuals had consented to give blood at different stages in their life, the team could identify those individuals that developed AML and then retrieve blood samples taken when they were healthy. They examined the leukaemia-associated genes to see if the patterns of mutation were different to those who had remained healthy.
Midway through the study, they discovered that scientists at the Princess Margarete Cancer Centre, University in Toronto and the Weizmann Institute had also tapped into the same resource to examine leukaemia gene mutations and rearrangements. They were able to merge the two studies to generate unambiguous results.
What was the outcome?
It was discovered that there are genetic patterns that define an individual’s course in developing AML. The presence of these unusual characteristic variants is different to that seen in normal patterns of ageing. However, despite the use of an existing large dataset, to get absolute clarity and a robust understanding of the early genetic changes that can lead to AML, they are looking to increase the numbers analysed from other cohorts. The long-term goal, when the team can reliably identify individuals at risk of developing AML, will be trials of population screening programmes and to investigate interventions to slow or prevent eventual AML emergence.