A blood test could predict the risk of developing leukaemia in older people years in advance by showing changes in blood cell production, according to a new research paper. Image By identifying those most at risk, it should be possible in the future to offer preventive or early treatment to improve patient outcomes, experts said. Leukaemia is often the result of a disturbance in the fine balance of blood cell production, in which new cells are made and old blood cells die. As we age, mutations in blood stem cells can cause the altered cells to have a growth advantage over other blood cells and outnumber them, which is called a fitness advantage. Studying the changes Researchers from the Universities of Edinburgh and Glasgow investigated how changes in fitness advantage that occur in blood production could provide clues to leukaemia risk depending on the type of mutation that occurs. The Lothian Birth Cohorts 1921 and 1936 are longitudinal studies of brain, cognitive and general ageing which have followed up individuals every 3 years between the ages of 70 and 82 for the 1921 cohort and the ages of 79 to 92 for 1936. We measured changes in the blood samples of 83 older individuals of the Lothian Birth Cohorts, taken every three years over a 12-year period. Using the combined knowledge of mathematicians, biologists and genome scientists, we set out to understand what these changes mean for our risk of developing leukemia as we grow older. Dr Tamir Chandra, Chancellor’s Fellow at University of Edinburgh's MRC Human Genetics Unit Mutations The team then combined this complex genomic data with a machine learning algorithm to link different mutations to different growth speeds of blood stem cells carrying those mutations. It was found that certain mutations gave stem cells measured in people without leukaemia distinct fitness advantages - this can then be used to predict how fast the mutant cells will grow, which determines leukaemia risk. The team say that due to the limited sample size of the current study, further research is needed to validate these findings in a larger population. To understand leukemia risk, we need to consider the balance between the different cells involved in blood cell production and how this balance changes as we grow older. By linking genomic data with machine learning we have been able to predict the future behaviour of blood cells based on the mutations they develop. Dr Linus Schumacher, Co-lead author and Chancellor’s Fellow at the Centre for Regenerative Medicine of the University of Edinburgh These findings have been published in the journal Nature Medicine. This research was funded by the Medical Research Council, Leukemia UK and Cancer Research UK. The Lothian Birth Cohort receives funding from Biotechnology and Biological Sciences Research Council, the Economic and Social Research Council, Age UK, Wellcome, the Royal Society, the Medical Research Council and the University of Edinburgh. Related Links MRC Human Genetics Unit Dr Tamir Chandra profile Dr Linus Schumacher profile Longitudinal dynamics of clonal hematopoiesis identifies gene-specific fitness effects This article was published on 2022-11-03
