Promising new approach discovered to treat leukemia

Promising new approach discovered to treat leukemia
Promising new approach discovered to treat leukemia

A group of researchers discovered a promising new approach to treating leukemia by disarming a gene that is responsible for tumor progression. That gene, Brg1, is a key regulator of leukemia stem cells that are the root cause of the disease, its resistance to treatment, and relapse.

Principal investigator Julie Lessard, PhD, and her colleagues at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal in Quebec, Canada, have spent the past 4 years studying the gene in collaboration with another research group at Stanford University in California. The results of their study were reported in Blood (2014; doi:10.1182/blood-2013-02-483495).

"When we removed the Brg1 gene, the leukemia stem cells were unable to divide, survive, and make new tumors. In other words, the cancer was permanently shut down," Lessard said.

One difficulty with targeting cancer stem cells is that many genes essential for their function are also essential for normal stem cells, and therapies targeting them can end up harming healthy stem cells as well.

"Strikingly, we showed that the Brg1 gene is dispensable for the function of normal blood stem cells, making it a promising therapeutic target in leukemia treatment," explained coauthor Pierre Thibault, PhD, also of IRIC.

The story showed striking results on laboratory animals and human leukemia cells but is still a long way from moving to the clinic.

"The next step will be to develop a small-molecule inhibitor to successfully block Brg1 function in leukemia, thus demonstrating the clinical relevance of this discovery," said Guy Sauvageau, MD, PhD, FRCP, also of IRIC and clinical hematologist at the Hôpital Maisonneuve-Rosemont in Montreal.

The group is now performing experiments to identify such drugs that can disarm the Brg1 gene, thereby stopping leukemia stem cells from generating malignant cells.

Cancer stem cells appear to be more resistant to radiotherapy and chemotherapy than the 'bulk' of the tumor and, therefore, are often responsible for cancer relapse. As such, inhibiting residual leukemia stem cells from dividing is the key to obtain irreversible impairment of tumor growth and long-term remission in patients.

"Our recent studies identified the gene, Brg1, as a regulator that governs the self-renewal, proliferative, and survival capacity of leukemia stem cells. Therefore, targeting the Brg1 gene in leukemia stem cells may offer new therapeutic opportunities by preventing the disease from coming back," Lessard concluded.

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