New test predicts whether blood cancer responds to therapy

UNSW medical researchers have developed a new way to predict whether patients with the blood condition myelodysplastic syndrome will respond to treatment.

A new method developed by UNSW Sydney medical researchers offers a way to predict whether patients with the blood condition myelodysplastic syndrome will respond to treatment.

Myelodysplastic syndrome (MDS) is characterised by impaired peripheral blood cell production and abnormal bone marrow, and more than 1400 people in Australia are diagnosed with the disease each year. MDS is much more common in older individuals and, if left untreated, the prognosis can be very poor.

Bone marrow transplantation could cure MDS. But this is an invasive procedure that is often not tolerated by older people. The best alternative is the drug azacitidine (AZA), which can improve blood production and decrease the likelihood of MDS progressing into leukemia.

“About half of MDS patients will not respond to AZA, with few alternatives for those who fail treatment,” says UNSW Research Fellow Dr Ashwin Unnikrishnan.

“Also, it takes about four to six months before we can tell if someone is responding to AZA treatment, at which point months of futile treatment has been given to those who are resistant to it.”

To address this issue, UNSW Medicine researchers led by Dr Unnikrishnan and Professor John Pimanda set out to develop a new quantitative method to measure AZA in patients receiving the treatment, to predict their response.

This method builds on their recent discovery that increased cell cycle quiescence of blood cells is a characteristic of patients who fail to respond to AZA treatment.

“The new method, called AZA-MS, utilises a cutting-edge technique known as mass spectrometry to measures the different forms of AZA inside blood cells of patients – such as the AZA molecules that are incorporated into the DNA or RNA,” says Dr Unnikrishnan.

“This development was very much an interdisciplinary effort involving researchers in the stem cell laboratory at the Lowy Cancer Research Centre and mass spectrometry experts at the Mark Wainwright Analytical Centre,” he says.

The team’s discoveries using AZA-MS are published in the journal Leukemia and reveal that MDS patients who do not respond to AZA treatment incorporate less AZA molecules in their DNA, compared to people who do respond. These findings are consistent with the team’s hypothesis that increased cell cycle quiescence of blood cells is a key driver of resistance to AZA treatment.

“These findings are really exciting because AZA-MS now allows us to identify early on which patients will not respond to AZA,” says Dr Unnikrishnan.

In early 2018, the AZA-MS method, along with another related test, will be used in a UNSW clinical trial led by Professor Pimanda, together with the pharmaceutical company Celgene and multiple hospitals in New South Wales.

“One of the benefits of using the test in this trial is that it will help determine if people respond to AZA tablets, compared to the currently used injectable form,” says Professor Pimanda.

Dr Unnikrishnan says: “The hope is that the AZA tablets will be effective for people who would otherwise not respond to AZA and that the overall response to AZA improves.

“The clinical trial will also allow us to collect samples that will enable us to answer long-term questions aimed at improving treatment in MDS.

“Altogether, we are hoping to fundamentally improve treatment for MDS patients, with the test as a big step towards personalised therapy,” he says.

This study was funded by the National Health and Medical Research Council, Leukaemia Foundation, and Anthony Rothe Memorial Trust.

(Source: UNSW Sydney, Leukemia)