The discovery of a stem cell that evades therapy and may trigger acute leukemia and relapses among patients in remission could potentially help stop the disease in its early stages, according to a new study from the Princess Margaret Cancer Centre that builds on research by a former Israeli medical resident.
Dr. Liran Shlush currently works at Princess Margaret, but his leukemia research began when he was completing his internal medicine residency at the Rambam Medical Center in Haifa.
Shlush is now part of a team under the leadership of John Dick that began studying acute myeloid leukemia (AML) cells with a general curiosity, not knowing what they would find.
Dick’s team sequenced the genomes of AML samples and compared them with what was supposed to be a lineage of white blood cells unaffected by the disease.
That’s when they discovered a mutation in the gene DNMT3a in 25 per cent of AML patients. That mutation causes pre-leukemic stem cells to appear as though they are normal cells, but they grow at an abnormal rate.
“That was the ‘eureka moment,’” Shlush said.
Essentially, Dick’s team has discovered a stage that is a precursor to the appearance or reappearance of leukemia in a patient.
AML occurs when white blood cells mutate and divide too rapidly. When you look at them through a microscope, they’re actually composed of different sub-populations of cells that are genetically distinct, Shlush said.
It’s hard to diagnose leukemia early on, Shlush said, because its cells circulate in a patient’s bloodstream without any tangible or visible structure, such as a tumour, unlike many other forms of cancer.
“The patients [usually] come into the clinic with the full-blown disease,” Shlush said. “No one knows what is the first mutation that started it all, but now we have a genetic marker we can test.”
The team hopes its discovery will allow for earlier diagnoses and, therefore, increased survival rates.
All of the findings are very preliminary, Shlush emphasized. There aren’t any drugs to target the rogue cells yet, and it’s still extremely difficult to determine if people have them.
But the team’s discovery could pave the way to some really significant findings in the future, and perhaps even a cure.
For now, the researchers will continue to study the disease using their discovery as a starting point to advance personalized cancer medicine by identifying who might be at risk.