The body’s innate immune system, active from birth, is the first line of defense against viruses and other disease-causing pathogens. Using the vaccine as an example, after receiving a vaccine, pain, redness, or swelling may occur at the injection site. This response is a demonstration of how the immune system is activated, but it must also be turned off in time for the side effects to subside. Dr. Yuliang Wu (PhD) of USask Medical School and his team are investigating how a gene known as DDX41 contributes to this function of the immune system and how mutations in the gene can lead to two life-threatening blood cancers. : myelodysplastic syndromes (MDS). and acute myeloid leukemia (AML).
The basic function of DDX41 was discovered in 2011. Research has identified that the gene probably plays a role in the development of blood cancer when the innate immune pathway is deregulated. An important enzyme, known as cyclic AMP-GMP synthase (cGAS), is involved in the detection of viruses in cells and in eliciting an immune system response. However, cGAS is activated by DDX41-regulated DNA.
To better understand this process, the researchers conducted experiments that involved directly isolating the DDX41 gene and observing its behavior when exposed to viruses.
“We found that the DDX41 gene is needed for a cGAS-mediated immune response against viral DNA infections,” Wu said. “The DDX41 gene can cause the innate immune system to overreact, leading to the development of blood cancer. “The virus is just one of them, and what we mean is that the deregulated immune response causes cancer.”
The results provide a starting point for understanding the links between the immune system, genetics, and the two types of cancer. Wu’s goal is to find drugs targeting the DDX41 gene as a potential treatment for both blood cancers.
Wu said finding effective treatments is a priority for researchers, as both MDS and AML will be more common in older populations as their lifespan continues to lengthen.
“The next steps in this research are to identify molecules or chemical compounds with the potential to modulate the enzymatic activity of DDX41, and we could use them to activate or deactivate this pathway,” he said.
Several other researchers participated in the study, from USask, the University of Illinois at Chicago, and Kumamoto University in Japan.
The research was funded by the Natural Sciences and Engineering Research Council of Canada, the Canada Foundation for Innovation, the Cancer Research Society, the National Institutes of Health, the Canadian Cancer Society and the Health Research Foundation. of Saskatchewan.