Blood cancer biomarker discovered

An international team of scientists has discovered a biomarker that could help to unlock the medical mystery behind multiple myeloma — an untreatable blood cancer that affects mostly older Australians.

Multiple myeloma grows in the bone marrow and affects around 1800 Australians every year. Now, researchers led by QIMR Berghofer’s Professor Mark Smyth and Dr Kyohei Nakamura have found that a molecule called IL-18 suppresses the immune system to help create a bone marrow environment where cancer is more likely to grow.

The team’s study analysed the impact of IL-18 on 152 patients with multiple myeloma and found strong evidence that high levels of the molecule were associated with poorer survival. The results were published in the journal Cancer Cell.

Professor Smyth said IL-18 is responsible for promoting the immune suppressive function of a particular kind of white blood cell (granulocyte) in the bone marrow. The resulting suppression hinders another kind of immune cell, known as a T cell, from doing its job of finding and destroying cancer cells.

“IL-18 has traditionally been recognised as a growth factor for immune cells, because it was thought to promote the activity of the white blood or ‘natural killer’ cells that protect us from infection and cancer,” he said.

“We’ve turned that thinking on its head with our discovery that IL-18 is actually a pro-tumour factor, which causes virtually the opposite effect.

“IL-18 is critical in the progression of multiple myeloma by enabling one part of the immune system to suppress another.”

Professor Smyth said bone marrow IL-18 levels are a potential biomarker for predicting a person’s disease prognosis as well as a potential target for new multiple myeloma treatments. He explained, “Practically speaking, the higher a person’s IL-18 levels in the bone marrow, the greater the likelihood their immune system is suppressed. That means their prognosis is not as good.”

Dr Nakamura said the findings could one day influence the way patients are treated for multiple myeloma, noting, “If a person’s prognosis is not as good because they have higher levels of IL-18 in the bone marrow, a doctor might choose to treat the patient more aggressively.”

He added that the discovery is vital to building a better understanding of the molecular processes that cause the inflammation in the bone marrow that leads to the development of multiple myeloma.

“This will help us to determine whether this biology is unique to the bone marrow and multiple myeloma or whether it is also present in other cancers,” he said.

There is even the potential to one day work with pharmaceutical partners interested in targeting IL-18 with a unique antibody or small molecule inhibitors, Dr Nakamura concluded.