MAY 27, 2022 4:22 PM PDT

How Certain Genetic Mutations Can Increase the Risk of Blood Cancer

WRITTEN BY: Carmen Leitch

From birth, our immune system is ready to spring into action to protect us from pathogenic invaders. Like the rest of the immune system, the innate immune system has to be carefully controlled, and the body has to turn it off when its job is finished; uncontrolled or dysfunctional immune responses can lead to serious disease. Researchers have now learned more about how a gene called DDX41 is involved in the function of the immune system, and the mutations in that gene, which have the potential to cause blood cancers known as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The findings have been published in Cell Reports.

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Previous work has shown that DDX41 helps suppress the growth of tumors, and that mutations in DDX41 increase a person's risk of AML. Studies have suggested that blood cancer risk is raised because mutations in DDX41 cause disruptions in innate immunity.

DDX41 is a molecule known as an RNA helicase, and it performs a variety of functions; it helps control the expression and splicing of other genes. One study has indicated that DDX41 is involved in the expression of over 900 other genes, including immune response genes.

An enzyme called cyclic AMP-GMP synthase (cGAS) can detect pathogenic invaders. When that happens, it triggers the activity of interferon genes, and the (STING)-type I interferon pathway. The cGAS enzyme is activated by DNA, which gets regulated in turn by DDX41.

To learn more about this process, scientists studied DDX41 activity when it was exposed to viruses.

"We found that the DDX41 gene is required for a cGAS-mediated immune response against DNA viral infections," said Dr. Yuliang Wu, Ph.D. of the University of Saskatchewan. "The DDX41 gene can cause the innate immune system to respond excessively, leading to blood cancer development."

Wu noted that this research has not indicated that viruses cause cancer. The immune system must constantly respond to various pathogens, including viruses, and when pathways that are involved in the immune response are not correctly regulated, that may lead to cancer.

This work can help us understand how that happens for DDX41 mutations and MDS/AML. Wu is hopeful that drugs targeting DDX41 could help treat those blood cancers, especially as the rates of those cancers rise in an aging population.

Sources: University of Saskatchewan, Cell Reports

About the Author
Bachelor's (BA/BS/Other)
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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