Stem Cell Subtypes Discovered: Could Lead To Improved Leukemia Treatments

Published in the August edition of Cell Stem Cell, the study by Dr. Connie Eaves and her team at the BC Cancer Agency’s Terry Fox Laboratory identified distinct subtypes of blood stem cells in the adult mouse. Each stem cell subtype behaves uniquely and produces different types of mature blood cells in a transplant setting.

“For the first time, we have been able to show that in mice there are different types of blood stem cells that can perpetuate themselves for a lifetime,” says Dr. Brad Dykstra, first author of the paper. “This could have important implications for understanding human leukemia since many leukemias are thought to arise from a single blood stem cell.”

If this discovery holds true in humans, it could explain why certain leukemias are harder to treat. Transplanting specific stem cell subtypes that produce different amounts of mature blood cells might also make bone marrow transplants more effective and improve outcomes for patients.

Blood stem cells are highly versatile, self-sustaining cells that can generate multiple types of other specialized cells that make up our blood, including immune cells, platelet-producing cells, red blood cells and other infection-fighting white cells.

“This discovery has really turned the field on its head,” explains Dr. Connie Eaves, Director of the BC Cancer Agency’s Terry Fox Laboratory. “For many years, it has been assumed that all blood stem cells are identical and that the differences in their behaviour are determined by the stimuli they receive from their environment and a differential partitioning of limited internal components.”

“Our evidence that individual blood stem cells have intrinsic differences will now force a major change in how we will have to investigate normal blood cell development and leukemogenesis at a molecular level,” adds Dr. Eaves.

The discovery was made by isolating a tiny sub-population of adult mouse bone marrow that is highly enriched in blood stem cells and then transplanting them as single cells into irradiated mice whose own blood cells could be distinguished from the progeny of the injected cell. The power of a single cell transplant is that all of the cells it subsequently produces can be tracked throughout the entire post-transplant period.

The next step, currently underway at the BC Cancer Agency, an agency of the Provincial Health Services Authority, is to isolate the different subtypes of blood stem cells and study the genes and proteins that dictate their behaviour.

The BC Cancer Foundation provides core funding for research at the BC Cancer Agency. Funding for this research was also provided by the National Cancer Institute of Canada, the Terry Fox Foundation, the Michael Smith Foundation for Health Research and Genome BC/Genome Canada.

In 2007, an estimated 493 British Columbians will be diagnosed with leukemia and 326 will die of it. One in 99 females and one in 71 males is expected to develop leukemia during their lifetime.