Leukaemia gene faults accumulate with age

In collaboration with the Press Association

Genetic mutations in blood cells that could develop into leukaemia become "almost inevitable" as people get older, new research suggests.

"We know that the risk of developing most types of cancer increases with age but  relatively little is known about exactly how or why this happens." - Dr Kat Arney, Cancer Research UK

A study by scientists at the Wellcome Trust Sanger Institute found more than 70 per cent of people aged over 90 had blood cells with some of the same DNA alterations found in the cancer.

Dr Kat Arney, science communications manager at Cancer Research UK, said it would be "fascinating" to see if the technique could be applied to other kinds of cancers.

Dr George Vassiliou, senior author from the Sanger Institute and Cambridge University Hospitals NHS Trust, said: "These mutations will be harmless for the majority of people but for a few unlucky carriers they will take the body on a journey towards leukaemia."

"We had suspected people had these mutations, but didn't expect they would be an almost inevitable consequence of ageing.

"There is one warning for the future, if there was a significant extension of life expectancy then there could be a significant increase in leukaemia," he added.

However, he said, more work was needed to work out how the mutations' presence translated into risk of developing the disease.

"We don't know what percentage of people would go on to develop leukaemia, it might be one in 1,000 or even one in 100 or more and that would have a dramatic impact."

The study, published in the Cell Reports journal, analysed blood samples from 4,219 healthy people, using a highly sensitive technique called ‘ultra-deep sequencing’ to detect DNA changes.

They found that up to 20 per cent of those aged between 50 and 60 had genetic defects associated with leukaemia. This figure rose dramatically as people got even older, to around 70 per cent.

However, a mutation in a key gene that kickstarts the transition into leukaemia, known as NPM1, was not detected in any of the participants, suggesting the need for an additional genetic trigger for the disease.

Dr Arney commented: “We know that the risk of developing most types of cancer increases with age. But, although this risk is assumed to be down to the build-up of mistakes in our DNA over many years, relatively little is known about exactly how or why this happens.

“This is a fascinating and important study highlighting how the genetic makeup of blood cells changes as we get older, and may contribute to the development of leukaemia. It will be interesting to see if this kind of technique can be applied to other types of cancer too.”

Dr Thomas McKerrell, joint author of the study, said: "Leukaemia results from the gradual accumulation of DNA mutations in blood stem cells, in a process that can take decades.

"Over time, the probability of these cells acquiring mutations rises. What surprised us was that we found these mutations in such a large proportion of elderly people.

"This study helps us understand how ageing can lead to leukaemia, even though the great majority of people will not live long enough to accumulate all the mutations required to develop the disease."