Multiple myeloma patients with high levels of the EZH2 enzyme have shorter survival times, regardless of the treatment they receive, a British study reports.
EZH2 plays a key role in the normal development of immune B-cells. But scientists have also linked it to the development and progression of myeloma.
Researchers at Uppsala University in Sweden had previously tied abnormal chemical modifications in DNA-associated proteins known as histones to the development of multiple myeloma. They determined that EZH2 was involved in the histone modification.
A research team at the Institute of Cancer Research in London decided to look at samples from more than 1,500 multiple myeloma patients to see if they could find a correlation between EZH2 levels and patient outcomes.
They discovered that patients with higher levels of the enzyme were less likely to continue to respond to treatment than those with lower levels. Patients with higher levels also had lower survival rates, regardless of the treatment they received, the researchers said.
To better understand this association, the team examined the role that EZH2 plays in normal myeloma cells and myeloma cancer samples. They used two chemical inhibitors to block the enzyme’s activity.
Cancer cells treated with the inhibitors were unable to proliferate and died. That’s because lack of the enzyme prevented genes involved in cell division from performing this task.
Overall, the results suggested that EZH2 is a critical regulator of genes involved in myeloma cell division, contributing to multiple myeloma progression and aggressiveness. This means that targeting the enzyme could be a way to treat high-risk myeloma patients, the researchers said.
“Myeloma treatments over the past couple of decades have improved outcomes for many patients with the disease but they have not been very effective for patients with the most aggressive forms of myeloma,” Dr. Charlotte Pawlyn, a blood expert at the Royal Marsden Hospital, said in a news release.
“We have shown for the first time that EZH2 over-expression is associated with worse outcomes for patients with myeloma,” said Pawlyn, the first author of the study. “Our study demonstrates that EZH2 inhibition may be an effective therapeutic strategy for these patients, potentially even for those with high-risk disease.”
The study was funded by The Wellcome Trust, Myeloma UK, and Cancer Research UK. It received support from the National Institute for Health Research’s Biomedical Research Centre at The Royal Marsden National Health Service Foundation Trust and the Institute for Clinical Research.