Leukemia white blood cells, scanning electron microscope (SEM)

An international team of researchers, building upon earlier work of John Dick, Ph.D., senior scientist at Princess Margaret Cancer Centre, University Health Network, Toronto, has developed a method of blood analysis that can predict healthy individuals at risk of developing acute myeloid leukemia (AML).

Early detection of people at risk for developing AML could significantly improve the prognosis for people who eventually develop the disease, which has a high mortality rate due to late presentation of symptoms. According to Dick, the latest research helps to illuminate the ‘black box of leukemia’ to detail how the blood cancer first develops.

The study “Prediction of acute myeloid leukaemia risk in healthy individuals” was published earlier this week in the journal Nature.

“We have been able to identify people in the general population who have traces of mutations in their blood that represent the first steps in how normal blood cells begin on a pathway of becoming increasingly abnormal and puts them at risk of progressing to AML. We can find these traces up to 10 years before AML actually develops,” says Dick in a press release announcing the study results. “This long-time window gives us the first opportunity to think about how to prevent AML.”

The team, which comprised scientists from the Dick Lab at UHN, the Weizmann Institute of Science and the Clalit Research Institute in Israel, and the Wellcome Sanger Institute in Cambridge, England, among others leveraged data and blood samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The collaborators used stored blood samples from EPIC to look back in time to find which genetic changes were already present in the blood of people who eventually developed AML.

Sequencing the stored blood of 124 AML patients with 676 people who remained AML-free, the researchers discovered specific genetic changes that distinguished the AML patients from those without the disease. The intent is to use these genetic markers collectively to develop a screening test for AML.

“AML is a devastating disease diagnosed too late, with a 90 per cent mortality rate after the age of 65,” says Sagi Abelson, Ph.D., study author and post-doctoral fellow in the Dick Lab. “Our findings show it is possible to identify individuals in the general population who are at high risk of developing AML through a genetic test on a blood sample. The ultimate goal is to identify these individuals and study how we can target the mutated blood cells long before the disease actually begins.”

The current finding built upon Dick’s 2014 study that showed pre-leukemic stem cells could be found among all the leukemia cells present in an individual at the time of AML diagnosis. These pre-leukemic stem cells continue to function normally, but mark the potential first step in the pathway of cells that become increasingly abnormal and eventually resulting in AML.

“Our 2014 study predicted that people with early mutations in their blood stem cells, long before the disease appears and makes them sick, should be able to be detected within the general population by testing a blood sample for the presence of the mutation.” Dick says.

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