New research suggests that it is "almost inevitable" that one will develop genetic mutations associated with leukemia as they age.
Researchers estimated as much as 20 percent of people between the ages of 50 and 60, and over 70 percent of those over 90, possess blood cells with gene changes seen in cases of leukemia, the Wellcome Trust Sanger Institute reported.
To make their findings, a team of researchers looked at 4,219 individuals who did not have any evidence of blood cancer, and analyzed the earliest stages of cancer development in some of these patients using sequencing methods capable of detecting DNA mutations in as few as 1.6 percent of blood cells. The method allowed them to study 15 locations in the genome known to be altered in cases of leukemia. Comparisons with past research revealed the presence of pre-leukaemic cells in the general population is much higher than previously determined, and increases significantly with age.
"[Leukemia] results from the gradual accumulation of DNA mutations in blood stem cells, in a process that can take decades," said Dr. Thomas McKerrell, joint first author from the Wellcome Trust Sanger Institute. "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 aging 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."
None of the study participants were observed to have the NPM1 gene mutation, which is seen in up to 40 percent of acute leukemia cases. This findings suggest mutations in NPM1 act as "gatekeepers" for the cancer, and once a mutation in this gene occurs within a cell that holds pre-leukaemic mutations, the disease is able to progress.
"The significance of mutations in this gene is astonishingly clear from these results: it simply doesn't exist where there is no [leukemia]," said Dr. Naomi Park, joint first author from the Sanger Institute. "When it is mutated in the appropriate cell, the floodgates open and leukemia is then very likely to develop. This fits with studies we've conducted in the past in which we found that the gene primes blood stem cells for leukaemic transformation."
The findings could provide insight into the origins of cancer, which always begins with just a single small mutation.
"Ultra-deep sequencing has allowed us to see the very beginnings of cancer," said Dr. George Vassiliou, senior author from the Sanger Institute and Cambridge University Hospitals NHS Trust. "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 [leukemia]. We are now beginning to understand the major landmarks on that journey."
The findings were published in a recent edition of the journal Cell Reports.
