Blocking key gene may treat leukemia

Written by PTI | Toronto | Updated: Feb 14 2014, 18:42pm hrs
LeukemiaBrg1 gene is a key regulator of leukemia stem cells that are the root cause of the disease, resistance to treatment and relapse. Thinkstock
Scientists have discovered a promising new approach to treat leukemia by disarming a key gene that is responsible for tumour progression.

The gene, known as Brg1 is a key regulator of leukemia stem cells that are the root cause of the disease, resistance to treatment and relapse.

Julie Lessard, principal investigator and her colleagues at the Institute for Research in Immunology and Cancer (IRIC) of Universite de Montreal, Canada have spent past four years studying the gene.

"When we removed the Brg1 gene, the leukemia stem cells were unable to divide, survive and make new tumours. 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," said Pierre Thibault, co-author of the study.

The study showed striking results on laboratory animals and human leukemia cells but is still a long way from being transposed into the clinic, researchers said.

"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, chief executive officer and principal investigator at IRIC and co-author of the study.

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 tumour 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 tumour 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.

The study was published in the journal Blood.