Finding cancer before it grows and spreads is usually important in treating it successfully. But some cancers don’t have noticeable symptoms, making it difficult to diagnose them early.
One such cancer is acute myelogenous leukemia (AML). While serious symptoms can appear quickly, research suggests that the mutations that lead to AML quietly accumulate in blood cells for years before a final push transforms them into cancer cells, and importantly, it may be possible to detect this “pre-AML” phase.
A large international team of researchers, including a group led by Canadian Cancer Society-funded researcher Dr John Dick, studied whether they were able to distinguish cells with pre-AML from those with age-related clonal haematopoiesis (ARCH), a condition where mutations associated with AML also accumulate in blood cells but do not lead to cancer. The researchers wanted to gain a better understanding of the mutations in both AML and ARCH and use this information to determine whether it is possible to identify people at high risk of developing AML.
Key differences found in genetic makeup of pre-cancer cells
The researchers analyzed genetic material of blood cells from people who went on to develop AML, as well as healthy people in order to understand the differences between them.
On the surface, pre-AML and ARCH blood cells have many similarities, but the researchers found key differences related to the number and types of mutations. Pre-AML samples had much higher frequency of mutations, as well as larger populations of mutated cells than non-cancer samples. Importantly, they also found that pre-AML cells were more likely to carry gene mutations often found in cancer, while a few genes commonly mutated in ARCH actually seem to lower the risk that AML will develop.
The researchers were able to develop a computer model that included information from blood cells – specifically the number and frequency of genetic mutations – to predict whether an individual is likely to develop AML. But given that AML is relatively rare, it is important to narrow down the people at highest risk who should undergo this genetic test rather than to screen large populations.
Standard blood measurements may predict leukemia risk
To help identify a high-risk population that would benefit from targeted screening, the researchers studied whether a standard bloodwork measurement of blood cell size is associated with a risk of AML.
They found that this measurement, along with other clinical measurements such as reductions in red and white blood cell counts, were often abnormal several years before AML was diagnosed. This information allowed them to predict the people who would develop AML 6 to 12 months in the future.
Although a screening test for AML is a long way off, this research suggests that a strategy that combines genetic testing with standard blood testing could be an effective way to screen for people at high risk of AML. Easily accessible clinical information from bloodwork can identify a small population of people at highest risk of AML, who can then undergo genetic analysis to look for key cancer mutations. Those who are likely to develop AML can be monitored closely, so that when cancer does develop, it can be diagnosed early and treated more successfully.
Eileen Hoftyzer, BSc