According to a study published in the journal Cell Reports, it's possible for the disease not to manifest but gene mutations associated with leukemia almost inevitably develop as a person ages. By the time an individual goes beyond 90 years old, their blood cells will show the same genetic changes characteristic of leukemia despite not having any history of the cancer.
Thomas McKerrell from the Wellcome Trust Sanger Institute and colleagues used a sensitive type of sequencing method that allows for detecting mutations in the DNA in just 1.6 percent of blood cells to investigate cancer in its early stages of development. Specifically, they analyzed 15 spots in the genome that leukemia has been known to alter. By comparing the results of their work with other studies, the researchers found that pre-leukemia cells are more common in the general population than thought previously and prevalence dramatically increases with age.
"Leukemia results from the gradual accumulation of DNA mutations in blood stem cells, in a process that can take decades," said McKerrell.
Mutations piling up as time passes explains why leukemia-like results become more evident as people age. The older a person is, the more time the mutations have had to grow, leading to higher risks of the disease actually developing.
Researchers also discovered that mutations in the genes SRSF2 and SF3B1 were exclusive to 70-year-olds. This suggests that some mutations grow better later in life, maybe because they have less competition. This exclusive activity in the SRSF2 and SF3B1 genes is also an explanation for why leukemia-like conditions called myelodysplastic syndromes appear almost entirely just in the elderly.
None of the research subjects also showed mutations in the NPM1 gene, which is the most common attributed to leukemia, occurring in 40 percent of cases of the cancer. This surprising result hints that instead of actually causing the cancer, NPM1 acts more as gatekeepers. Once a mutation occurs in a cell with all the right pre-leukemia conditions, the floodgates open and the cancer rapidly develops.
Leukemia is a convenient model to use in researching how cancer begins, as blood samples are easier to acquire than tissue ones. With every cancer starting out from one mutation in a single cell, the study has made it possible for scientists to observe how the first mutations accumulate to result in the disease.
Other authors who contributed to the study include George Vassiliou, Naomi Park, Ignacio Varela, Thaidy Moreno, Willem Ouwehand, Carolyn Grove, Eleftheria Zeggini, Hannes Ponstingl, Duncan Forsyth, Jonathan Stephens, Roland Rad, Charles Crawley, Joanna Baxter, Jenny Craig, Clare Hodkinson, Mike Scott and the Understanding Society Scientific Group.
