A Children’s Medical Research Institute researcher has discovered an explanation for the link between one gene mutation often found in leukaemia and its resistance to chemotherapy and radiation treatment.
Dr Daniel Speidel’s work on mutations in the RUNX1 gene was published in Cancer Research late last month (October). It was the result of several years of work which began when he was working at Hamburg in Germany.
There has long been an association between mutations in the RUNX1 gene and poor prognosis for patients receiving chemotherapy, in diseases such as Acute Myeloid Leukaemia and other blood cancers. Now Dr Speidel has been able to explain the connection.
‘’I’ve always wanted to understand why some cancer patients react to chemotherapy but others do not,’’ he said. “My big theme is understanding what causes success or resistance to treatment at the molecular level."
"When it comes to Acute Myeloid Leukaemia, it is really nasty. Around 75 per cent of patients die within five years. It is also devastating in children. We knew that those with RUNX1 mutations had a particularly poor prognosis because their cancer is resistant to chemo, but we needed to understand why, so we can finally do something about it.’’
Dr Speidel found that RUNX1 is directly involved in the response of leukaemia cells to treatments such as chemotherapy or radiation. The gene regulates the blood cells, helping them to die during treatment, but only if the gene is not mutated.
“What we aim for with chemotherapy is to make cancer cells ‘commit suicide’,’’ he said. “And we found that RUNX1, if the gene is normal, helps the cells to die. If there is a mutation – RUNX1 can’t do that. Therefore, the chance of a successful cure is lower’’
In Australia, approximately 900 people are diagnosed with Acute Myeloid Leukaemia every year. Around 60 per cent turn out to be resistant to chemotherapy. Dr Speidel said his data suggests that the development of drugs that target RUNX1 may assist patients.
“The more we understand what causes therapy resistance, the better we can develop drugs that target that mechanism,’’ he said. “We could also learn which patient is more likely to respond to treatment. If we knew a patient is unlikely to respond to treatment, it would give people choices. Maybe we could spare them standard chemo and focus on alternative treatments.’’
Dr Speidel’s work was published in the journal Cancer Research as a “priority report’’ – a category reserved for short research papers of high impact, significance and timeliness.
The work of Dr Speidel at Children’s Medical Research Institute has been possible with the support of the Jeans for Genes campaign, the Anthony Rothe Memorial Trust, and Tour de Cure who he said have been “fantastic’’.
The original research publication can be found at Cancer Research’s website: http://cancerres.aacrjournals.org/cgi/content/abstract/0008-5472.CAN-17-0319
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