CAMBRIDGE (The Thursday Times) — The first genetic mutation behind acute myeloid leukaemia, an aggressive blood cancer, often appears more than 50 years before the disease is diagnosed, according to a study published in the journal Nature on Wednesday.
Researchers at the University of Cambridge and University College London used blood samples given every year by women in a long-running UK screening trial as a “fossil record” of how the disease developed. In two-thirds of the cases they studied, the first cancer-driving mutation had been acquired before the age of 20.
The team examined samples from 47 women who later developed the disease, at an average age of 72, and compared them with 46 women who stayed free of blood cancer. The samples came from the UK Collaborative Trial of Ovarian Cancer Screening, in which about 50,000 women gave blood every year for up to 11 years.
Slow growth, then a sprint
After the first mutation, the affected cells grew slowly for decades, taking years to double in number. Each further mutation made them grow two to three times faster, and cells carrying four cancer-driving mutations doubled in a matter of weeks.
That growth turned out to be remarkably predictable. “Once a clone is established, its growth rate today tells you where it will be years, even decades, from now,” said Professor Jamie Blundell of Cambridge’s Early Cancer Institute, who led the study.
In at least a third of the cases, a single group of mutated cells had come to dominate the blood years before diagnosis. No such pattern was seen in the women who stayed healthy, and data from the UK Biobank linked it to a much higher risk of the disease.
A window for prevention
Acute myeloid leukaemia affects about 2,700 people a year in the UK, and only about one in six patients survive five years after diagnosis. Many healthy older people carry blood cells with leukaemia-linked mutations, but only a few go on to develop the disease, and until now it has not been clear why.
The researchers say measuring how fast a mutated group of cells is growing could help doctors pick out those at highest risk, and that even slightly slowing that growth over a decade or more could sharply cut the chance of leukaemia. Testing whether that can be done safely is the team’s next step.
In about one in five cases, however, the expanding cells could not be detected until one or two years before diagnosis, which suggests some patients may have a much shorter warning period.
