High Enzyme Levels Signal Shortened Survival in Multiple Myeloma

12/25/17

High levels of a specific enzyme are linked with lower survival rates in patients with multiple myeloma, according to a new study published in Nature Communications (doi: 10.1038/s41467-017-01890-w).

“Despite new therapies, it’s virtually inevitable that a patient with multiple myeloma will experience relapse of the disease at some point,” said senior author Catriona Jamieson, MD, PhD, professor of medicine, University of California San Diego, in a press release (December 5, 2017). “That’s why it’s exciting that this discovery may allow us to detect the disease earlier and address the root cause.”

Over a 3-year period, 162 patients with low ADAR1 levels in tumor cells survived significantly longer than 159 patients with high ADAR1 levels, according the study. More than 90% of patients with low ADAR1 levels were alive more than 2 years after diagnosis compared with fewer than 70% of patients with high ADAR1 levels.

After transferring multiple myeloma patient tissue to mice to create an animal model, researchers discovered 2 events that seemed to activate ADAR1: a genetic abnormality plus inflammatory cues from surrounding bone marrow tissue. Silencing the ADAR1 gene, however, reduced multiple myeloma generation, the press release reported.

Dr Jamieson and colleagues are now testing inhibitors of the molecule JAK2, which affects ADAR1 activity, for their capacity to destroy cancer stem cells in multiple myeloma models. Several JAK2 inhibitors are already used to treat other types of cancer.

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“Several major advances in recent years have been good news for multiple myeloma patients, but those new drugs only target terminally differentiated cancer cells and thus can only reduce the bulk of the tumor,” said Dr Jamieson. “They don’t get to the root cause of disease development, progression and relapse — cancer stem cells — the way inhibiting ADAR1 does. I like to call our approach ‘precision regenerative medicine.’”—Jolynn Tumolo