TORONTO - Imagine if scientists could peer into the blood and see the very first aberrant cells that will give birth to leukemia and then watch as the disease slowly progresses and takes over the body.
Well, Canadian researchers have done just that - converted normal human blood cells into leukemia stem cells, then transplanted them into lab mice and witnessed the disease unfold.
"You can study certain things about human cancer by studying the cancer itself," said principal researcher John Dick, a stem cell biologist at Princess Margaret Hospital in Toronto. "But the one thing you can't study is what were the sequence of events that happened in the months and years before that process that actually led to that disease."
The groundbreaking research involved infecting cells from umbilical cord blood with a virus engineered to carry one of the genes known to cause certain types of leukemia. The genetic alteration created primitive leukemia stem cells, which were then injected into specially bred lab mice.
All of the animals - bred with no immune system, so their bodies do not reject human cells - developed leukemia with the same characteristics and patterns experienced by people with the disease, say the researchers, whose study was published Thursday in the journal Science.
"We actually created leukemia stem cells," said Dick. "And we could show that they actually arose, at least in this model, from a very primitive cell."
"So what we were watching in front of our eyes was the evolution of how the leukemia stem cells first were generated and then how they continued to evolve or become more and more abnormal."
Stem cells are like master cells that can give rise to different offspring. Normal stem cells can produce any kind of tissue, from skin to heart to brain; cancer stem cells are the progenitors of malignant tumour cells.
Dick said this window into leukemia's development will allow scientists to ask - and hopefully answer - some "very interesting questions."
Those include: Whether the seeds for acute leukemia that occurs in children are sown during fetal development? Is the childhood disease different from that in adults? In which cell type does leukemia arise? And which genes are involved and "in which order do they have to operate?"
As well, understanding how leukemia advances from the moment of its conception could aid the development of drugs that would stop the process before it advances too far, he said.
Commenting on the work, the president of the Canadian Institute for Health Research said the study demonstrates that identifying cancer stem cells is critical to understanding how a malignancy evolves and also suggests a new target for future chemotherapy.
"These stem cells are kind of the kings in a chess game," Dr. Alan Bernstein explained Thursday from Ottawa. "What we're inching towards - and this paper is a big step towards that - is an appreciation that it's actually important to know what the king is doing and where the king is."
"So capturing the king is going to be key in winning the battle against cancer," said Bernstein, who believes that finding new drugs to knock over cancer stem cells will be the next major advance in achieving checkmate over the disease.
Dr. Donna Hogge, a senior scientist at the B.C. Cancer Agency, called the research by Dick and his team "very exciting."
"What's new and different is they've actually been able to take a specific gene rearrangement that we have known about for quite a number of years in human leukemias and been able to take that specific abnormality and put it back into normal human cells and show that it does in fact cause leukemia."
"In terms of, is this going to change the way we treat leukemia, I think the answer is no," Hogge, a member of B.C.'s leukemia bone marrow transplant program, said from Vancouver.
"It does create potentially quite good models of human leukemia that could potentially be used for drug testing" in the future, she said. "But by itself, this does not, obviously, suggest a new drug that would come out of it that might be helpful."
