24
Apr 2014
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JulieLessard IRIC 2-cropped

Gene that regulates leukemia will take time (and patience) to tame

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While patience is a virtue for most of us, it is an absolute prerequisite for stem cell researchers.

The recent news that scientists have identified a gene called BRG1 that appears to regulate leukemia stem cells marks an important advance in understanding the dread disease. It also signifies years of work by the team led by Dr. Julie Lessard at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal.

“About four years,” says Dr. Lessard, pictured left, one of Canada’s leading researchers in the field of hematopoiesis — the art of blood production.

Using mice as subjects, Dr. Lessard’s team found that removing the BRG1 gene left the leukemia stem cells and progenitors unable to survive, divide and make new tumors, permanently shutting down the cancer.  But while they are delighted with their findings, the researchers know they are in for many more years of work.

“We need to identify BRG1 inhibitors that will work in vitro (in test tubes and Petri dishes) and in vivo (with animals and humans),” says Dr. Lessard. “We believe that it is the ATPase activity that is the essential function we need to target for potential drug development, so that’s what we’re going after.”

In essence, that means finding small molecules that can stifle BRG1, the research equivalent to finding a needle in a haystack. Fortunately, IRIC is equipped with computer-driven high throughput screening to search their library of about 120,000 molecules for one that will do the trick. “We are hoping we can get there in the coming years,” she says.

Dr. Lessard’s findings further strengthen Canadian leadership in the field of stem cells and hematopoiesis. It was two Ontario Cancer Institute researchers — Drs. James Till and Ernest McCulloch — who first proved the existence of stem cells in the early 1960s while trying to find new treatments for leukemia. Dr. John Dick, of Toronto’s University Health Network, first identified tumour-initiating cancer stem cells in 1997.

What’s particularly intriguing about Dr. Lessard’s findings is that shutting down the BRG1 gene only appears to affect leukemia-generating stem cells. “Its function in the normal stem cell is rather modest. So you can take the gene out of leukemic cells and it will shut them down without shutting down the other stem cells you need to continue growth.”

While Dr. Lessard is excited about this project, she’s realistic about the amount of time and work involved.

“First of all, we have to have a very solid preclinical product to test in animals.  We think that a therapeutic window must exist. And this is what makes this study more interesting. It will be very exciting to explore in the coming years.”

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