New treatment idea discovered for leukaemia

Monday, 2 November 2020

Newcastle researchers have discovered a new way to kill leukaemia cells.

Dr Matt Dun

The research collaboration between the University of Newcastle, Hunter Medical Research Institute and Hunter Cancer Research Alliance has had its findings published in the leading international blood cancerjournal Leukemia.

Associate Professor Nikki Verrills, Dr Matt Dun and Dr Heather Murray employed sophisticated and innovative technologies to survey all potential treatment targets in many leukaemia patient samples simultaneously, revealing a new treatment idea for the most aggressive type of blood cancer, acute myeloid leukaemia (AML).

Current treatments for AML only see a quarter of patients survive five years past their diagnosis. AML develops when cells in the bone marrow acquire changes in their cell communication processes (collectively termed cell signalling). The cell signalling changes in AML cause the cells to grow and divide very quickly. Because of this, the cells do not properly develop into mature white blood cells and therefore do not work properly in fighting infections. The abnormal cells also accumulate and take over the bone marrow and blood system. So, assessing all active signalling processes in the leukaemia cells of AML patients, provides us with the information necessary to develop new treatment approaches.

“Through collaborations with the University of Southern Denmark, we have established an advanced mass spectrometry proteomics platform at the University of Newcastle, which allows us to quantify the cell signalling processes that are active in any biological sample,” co-lead author Associate Professor Verrills said.

“This platform provides us with the tools to look beyond genomics, to identify treatment strategies that have long been invisible to clinical teams, exposing the trojan horse if you will, with the aim of improving treatment and outcomes for the 1,000 or so Australian patients diagnosed with AML every year,” co-lead author Dr Dun said.

Working closely with local haematologist and researcher A/Prof Anoop Enjeti, the team used this powerful proteomics platform to profile the activated signalling pathways in the leukaemia cells from AML patients, who were integral to this study.

Dr Murray said the team discovered that by using chemical compounds to simultaneously block the activity of FLT3 and DNA-PK, they were able to stop the growth of the leukaemia cells and cause the cells to die.

“Importantly, preclinical testing showed that the FLT3 and DNA-PK inhibitors are safe to administer and do not adversely affect normal cells,” Dr Murray said.

This exciting study has identified a potential new treatment paradigm for this devastating disease, which the team hope to soon test in clinical trials. It has also led to further funding from the National Health and Medical Research Council (NHMRC), and the establishment of the Hunter Leukaemia Program, to apply their novel proteomics platform to more patients for the discovery of further new treatments.

This work was carried out by Dr Heather Murray, as part of her PhD studies, and was led by Dr Matt Dun and A/Prof Nikki Verrills.

Paper: “Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia”

*This work has been supported the Cancer Institute NSW, the National Health and Medical Research Council, the Australian Research Council, HMRI and the Hunter Cancer Research Alliance (HCRA).

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