Photo supplied by: University of New South Wales
Epigenetic therapy in myelodysplasia (MDS) and chronic myelomonocytic leukaemia (CMML)
University of New South Wales | 2012 | Project Grant | $676,780
Team members: Dr Peter Campbell, Associate Professor Preethi Gunaratne, Dr Karen MacKenzie, Associate Professor Michael Buckley, Associate Professor Diego Miranda-Saavedra and Dr Jason Wong.
About half of the patients who receive drug treatment for Myelodysplasia (MDS) and Chronic Myelomonocytic Leukaemia (CMML)—types of blood cancer—do not respond and about half of those who do respond, relapse when on treatment.
‘On average eight people per 100,000 a year develop Myelodysplasia—a disorder affecting the development of blood cells that can lead to leukaemia.1’
Professor John Pimanda and his team at the Lowy Cancer Research Centre have developed a method of predicting whether a patient will respond to drug treatment or not.
‘There is an urgent need to identify predictors of response and therapeutic alternatives for patients with primary or secondary 5-Azacytidine (AZA) resistance,’ Professor Pimanda said.
‘We have developed a test that can now be applied in the clinical setting to predict which patients are likely or unlikely to respond to AZA treatment without having to receive months of potentially futile treatment.’
Professor Pimanda’s team has shown that the haematopoietic progenitor cells (immature blood cells) of patients who do not respond to AZA treatment proliferate less in comparison to patients who do respond.
‘Drug responsiveness can be predicted using flow cytometry—a biophysical laser cell-counting and protein detection method—using pre-treatment bone marrow samples,’ Professor Pimanda explained.
‘We have also developed a parallel test that could use peripheral blood to monitor drug response.’
‘Our explorations were born out of curiosity to explore processes that control cell proliferation and identity during blood development in the embryo and in maintenance of healthy adult blood stem cells, and how these systems fail in leukaemic cells,’ he said.
‘We now have a better understanding of the relationship between diseased blood stem cells and their function and are pursuing these leads to understand how mutated cells gain an advantage in our bone marrow.’
Professor Pimanda’s team is adapting the flow cytometry test to suit the machines in the clinical laboratory and has initiated a clinical trial to develop a drug response score that will utilise this and other markers to determine early response.
There is evidence to suggest that drug resistance has many causes and each broad type of resistance requires a different treatment strategy. Professor Pimanda and his team has gained significant insights into the molecular pathways that need to be activated for drug response and is pursuing these in the search for better alternatives.
1 Australian Institute of Health and Welfare (AIHW), 2017. Burden of cancer in Australia: Australian Burden of Disease Study 2011.