Research published in Nature by a team from the University of Cambridge and University College London (UCL) has used serial blood samples as a 'fossil record' to trace the step-by-step development of AML. By employing ultra-sensitive DNA sequencing and mathematical modelling, the scientists estimated when each mutation arose and how quickly the affected cells multiplied prior to diagnosis.
AML, an aggressive blood cancer affecting around 2,700 people annually in the UK, has a five-year survival rate of only about one in six. While many healthy older individuals carry mutations associated with leukaemia (clonal haematopoiesis), only a fraction develop the disease. This study, using samples from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), analysed 47 women who later developed AML and compared them with 46 women who remained cancer-free.
The findings indicate that in two-thirds of AML cases, the first mutation was acquired before the age of 20, followed by decades of slow cell growth. Each subsequent mutation accelerated this growth rate, with cells carrying four mutations doubling in weeks. The predictable expansion of these cell groups, known as clones, allows for future growth estimation based on current measurements.
In at least a third of AML cases, a clone dominated the blood years before diagnosis, a phenomenon termed 'somatic sweep'. This was not observed in cancer-free individuals. The research, confirmed with UK Biobank data, highlights these sweeps as a significant risk factor, often overlooked by standard genetic analysis.
“"Serial blood samples are a fossil record of the blood's evolution. They let us go back in time and reconstruct when each mutation arose and how fast it grew. What surprised us most is how predictable the growth of these clones is. Once a clone is established, its growth rate today tells you where it will be years, even decades, from now."
Professor Jamie Blundell, who led the study, expressed surprise at the predictability of clone growth, suggesting that slowing high-risk clones before diagnosis could substantially reduce leukaemia progression. Dr Caroline Watson, first author and Honorary Consultant Haematologist at the Cambridge Clonal Haematopoiesis Clinic, noted the decades-long build-up to AML and the potential for preventative treatments.
The study, funded by UK Research & Innovation and Cancer Research UK, also identified that in some cases, expanding mutated cell populations were only detectable one to two years before diagnosis, indicating a potentially shorter warning period. The team's next step is to test preventative treatments that safely and effectively slow clone growth in high-risk individuals.
Professor Usha Menon from UCL Institute of Clinical Trials and Methodology, highlighted the value of the UKCTOCS bioresource in studying cancer development and validating biomarkers for early detection, thanking the participants for their contribution.
