Using DNA samples from research unrelated to cancer, two teams of scientists have uncovered early, pre-cancerous genetic changes in the blood that are linked to increased chances of developing blood cancers such as leukemia, lymphoma or myelodysplastic syndrome.
The teams believe their findings open new avenues for research into early detection and prevention of blood cancer.
The studies – by teams from Harvard Medical School, the Harvard Stem Cell Institute (HSCI), the Broad Institute of MIT and Harvard, and Harvard-affiliated hospitals – are reported in two papers published in the New England Journal of Medicine.
Working independently of each other, the two groups of scientists uncovered a detectable, pre-cancerous state in the blood that features mutations that develop in a small number of genes known to be related to blood cancers.
The scientists think the mutations – which cells acquire over time – originate in blood stem cells.
Steven McCarroll, senior author of one of the papers and assistant professor of genetics at Harvard Medical School, says:
“People often think about disease in black and white – that there’s ‘healthy’ and there’s ‘disease’ – but in reality most disease develops gradually over months or years. These findings give us a window on these early stages in the development of blood cancer.”
The studies are unusual because they tackled the research from an unconventional direction. Most genetic research on cancer focuses on genomes of advanced cancers to find mutated genes.
But in these two new studies, the teams looked at somatic mutations – the copying mistakes in DNA that accumulate over time as cells divide and replicate – in DNA from blood samples of people who did not have cancer or blood disorders.
They found that a subset – some, but not all – of mutations known to feature in blood cancers were present in individuals who were 10 times more likely to develop blood cancer later in life, compared with individuals who did not have these mutations.
This cluster of pre-cancerous mutations – which is easily detected by DNA sequencing – is rarely found in the blood of people under the age of 40. It becomes more common with age and appears in more than 10% of people over the age of 70.
The scientists believe the mutations originate in blood stem cells, spurring mutated cells and their descendant clones to grow faster until they account for a larger proportion of the cells in a person’s blood.
They also suspect the early mutations wait for – and team up with – later mutations to drive the cells toward cancer.
Most of the mutations occurred in just three genes: DNMT3A, TET2 and ASXL1.
Both teams were keen to point out that there would be no benefit in testing for this pre-cancerous state – and there are no treatments available to address the condition – in healthy people.
However, they suggest the findings open new ways to research blood cancer that could lead to earlier detection and even prevention.
Prof. McCarroll, who is also director of genetics at the Broad’s Stanley Center for Psychiatric Research, says:
“The results demonstrate a way to identify high-risk cohorts – people who are at much higher than average risk of progressing to cancer – which could be a population for clinical trials of future prevention strategies. The abundance of these mutated cells could also serve as a biomarker – like LDL cholesterol is for cardiovascular disease – to test the effects of potential prevention therapies in clinical trials.”
Every 3 minutes in the US, a person is diagnosed with blood cancer, new cases of which are expected to account for over 9% of all new cancer cases in 2014, according to the Leukemia and Lymphoma Society.
In September 2014, Medical News Today learned of a study that uncovered a genetic network that drives an aggressive form of leukemia and its precursor – myelodysplastic syndrome – paving the way for new treatments.