Researchers have developed a new method that offers a way to predict whether patients with the blood condition myelodysplastic syndrome will respond to treatment. The study findings were published in the journal Leukaemia.

Myelodysplastic syndrome (MDS) is characterised by impaired peripheral blood cell production and abnormal bone marrow. 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 leukaemia.

About half of MDS patients will not respond to AZA, with few alternatives for those who fail treatment. To address this issue, the researchers set out to develop a new quantitative method to measure AZA in patients receiving the treatment, to predict their response. The 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. 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.

The team's discoveries using AZA-MS 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.

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. 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. Altogether, the team are hoping to fundamentally improve treatment for MDS patients, with the test as a big step towards personalised therapy.