Montreal, QC May 12, 2003 A discovery by Dr Guy Sauvageau, a researcher in the Institut de recherches cliniques de Montral, professor at Universit de Montral and hematologist at Maisonneuve-Rosemont hospital, could improve treatments for blood disorders and open up new avenues of research into cancer, as well as boost production of blood derivatives. The Montreal hematologist’s work was presented in recent issues of Nature and Cell – Immunity.
“The HoxB4 gene, located on chromosome 17 of the human genome, is able to increase stem cell reproduction exponentially,” says Dr Sauvageau. “We have shown that its presence, both in vitro and in vivo, can boost the number of cells produced by a factor of 1000.”
Stem cells, whose secrets are just beginning to be understood, are capable of regenerating themselves or differentiating into a living organ or tissue. “Every day, we produce billions of cells,” the researcher observes. “Yet the scores of stem cells we receive at birth remain unchanged throughout our lives. They go on renewing themselves, even while they produce new cells that are able to specialize.”
Currently, stem cells obtained from the bone marrow or umbilical cord are being grafted into patients suffering from a variety of blood disorders. But the transplanted cells are often too few in number, and factors that might cause them proliferate are still largely unknown. New research into the HoxB4 gene could change all that.
An abnormality noted in the drosophilia species led to the discovery of the HoxB4 gene. Some of these flies are born with a leg in place of an antenna. The phenomenon was well known to biologists, but Dr Sauvageau showed that the same genes (in particular HoxB4) induce proliferation of stem cells. This very unique property of HoxB4 could well lead to significant clinical applications. In fact, Dr Sauvageau’s team is working to develop an HoxB4 protein that could serve as a growth factor for stem cells.
In cancer biology, an emerging new theory says that a small group of “cancer” stem cells may be a factor in tumour growth. In the journal Nature, Prof Sauvageau and his student Julie Lessard present the result of their research on the Bmi-1 gene, which is essential for the proliferation of leukemic stem cells. “We provide proof that the proliferation potential of stem cells involved in leukemia is related to the presence of Bmi- 1," he says. "This gene could become a major new target for therapy in the treatment of leukemia, and perhaps even for other cancers.”
“This research has significant implications for the development of leukemia treatments. The discovery of a key role played by a gene in the growth of leukemic stem cells provides a potential target of attack. By destroying the developing leukemic cells, the seeds of the disease can be wiped out. The challenge is how to do this without destroying normal stem cells,” says Dr Marshall Lichtman, executive vice president for research and medical programs at the Leukemia & Lymphoma Society, which has provided support for Dr Sauvageau’s research.
These discoveries hold out promising new prospects for treatment. For example, the HoxB4 gene could make it possible to replicate products such as blood in a bioreactor. Through therapeutic cloning, it could also be used to treat genetic disorders. It may be possible to correct “errors” in the genetic code with healthy derivative cells generated by the application of HoxB4.
The research work that led up to the publication in Nature was funded by the Canadian Institutes of Health Research (CIHR) and the Leukemia and Lymphoma Society. The US National Institutes of Health (NIH) funded the research that resulted in the publication in Cell (Immunity).
Dr Sauvageau’s work will soon be continued in the new Cancer and immunology Institute at Universit de Montral.