Double discovery – game changer in quest to cure leukaemia
Research funded by the Leukaemia Foundation has made two groundbreaking discoveries in the quest to defeat one of the most aggressive forms of leukaemia.
Researchers at the Peter MacCallum Cancer Centre (Melbourne) have uncovered vital new leads on how to outsmart the deadly disease, based on how a form of leukaemia fights back against an innovative new treatment.
Discovery 1: Ability to grow AML cells in a laboratory dish
For the first time, Peter Mac’s Cancer Epigenetics Laboratory team has grown and maintained acute myeloid leukaemia (AML) stem cells in a laboratory dish. Until now, all studies on the stem cells of this deadly disease have had to occur in mice models in the laboratory.
Being able to grow and maintain leukaemia stem cells in a laboratory dish gives us unprecedented access and insight into how they work, so we can find new, faster, and better ways to target and destroy them. This is great news for the 900 Australians who will be diagnosed with AML each year.
Discovery 2: New understanding of how AML cells become resistant to chemotherapy
AML stem cells are particularly aggressive, insidious and nimble. Current treatments can have an impact on the disease for a time, but most people with this disease will become resistant to therapy and the disease will progress. With current treatments, on average, only 25% of people diagnosed with AML will live for five years.
Until now, we have not known if the AML stem cells became resistant to therapies, or if the micro environment within the bone marrow, where stem cells reside, protect the stem cells from chemotherapy. Knowing how AML stem cells respond when under attack by chemotherapy enables researchers to devise interventions to prevent the development of resistance, and therefore rid the body of the disease.
The research, published overnight in the premier scientific journal, Nature, shows how leukaemia stem cells react to a new treatment that is being used in an international clinical trial* underway at Peter Mac.
This promising treatment can effectively ‘turn-off’ cancerous genes in AML. The research found that resistance develops when the cells adapt to circumvent the drug and turn back on key cancer-driving genes through a previously under-recognised mechanism.
According to the lead investigator, Associate Professor Mark Dawson, a Leukaemia Foundation Senior Research Fellow, the double discovery will boost global understanding of AML, which affects more than 300,000 people globally.
“Our clinical trial is giving new hope to selected patients with aggressive forms of AML. However, the risk of resistance developing is common in any cancer treatment. Knowing precisely how that happens in advance puts us one step ahead in outmaneuvering the disease,” he said. “How broadly applicable our finding may be outside of the context of AML, time, as always, will tell,” Associate Professor Mark Dawson explained.
The findings build on more than 10 years of research and clinical work, initially undertaken at the University of Cambridge (UK) by Associate Professor Dawson. He is now a consultant haematologist and head of the Cancer Epigenetics Laboratory at Peter Mac.
In 2011, Associate Professor Dawson and the team in Cambridge were instrumental in the development of this class of epigenetic drugs called BET bromodomain inhibitors. These drugs alter the way DNA is packaged and deciphered, ultimately resulting in ‘switching off’ cancer causing genes.
This therapeutic strategy is very effective in pre-clinical models of aggressive leukaemias and Associate Professor Dawson now leads a first-in-class international clinical trial of these drugs in Australia, with the goal of increasing survival rates and advancing cures for aggressive blood cancers over the longer term.