The genes ‘KDM4C’ and ‘PRMT1’ ordinarily play a role in translating the genetic information in DNA into healthy cell functions. The researchers have shown, however, that during leukaemia development these enzymes are recruited to enable the transformation of blood cells into cancer cells. Crucially, these genes work in tandem and if either is not fully active, leukaemia is not able to develop.
In a report published in the journal Cancer Cell, the scientists used genetic tools to silence the two genes, as well as drugs to block their activity, in mice with AML. When either gene was silenced, the majority of the mice were still alive at the end of the 60-day experiment, whereas without treatment, the majority died in under 40 days. By blocking either gene’s activity with drugs, which is more relevant to how human patients would be treated, the survival times for mice with AML were also significantly extended.
Blocking PRMT1 meant half the mice were still alive after 48 days, compared to 36 days for mice who did not receive treatment. Strikingly, leukaemia development was even more effectively suppressed in mice with AML by using a drug to block KDM4C activity instead. All of the mice treated with a KDM4C blocker were still alive at the end of the experiments while the group without treatment succumbed to the disease.
The research was funded by the blood cancer charity Bloodwise with additional funding from Cancer Research UK.
Professor Eric So, who led the research at King’s College London, said: “The demonstration of how critical these genes are to cancer transformation and treatment could be highly significant for the design of new drugs. Further work is needed to develop and refine drugs to maximise their effects and so that they are suitable for patients. Clinical trials will then be needed to see how leukaemia patients respond to these drugs and how use of them can be optimised.”
AML is diagnosed in around 2,400 people each year in the UK. Treatment aimed at a cure still mainly consists of gruelling chemotherapy that is normally too toxic for patients over the age of 60. Currently only one in five patients will survive for more than five years after diagnosis.
Dr Matt Kaiser, Head of Research at Bloodwise, said: “Patients with acute myeloid leukaemia have not yet benefited from the new era of precision medicine that has taken place in many other types of leukaemia. While this research is at an early stage, the possibility of developing drugs that can specifically target the cancer cells, without the life-threatening side-effects of traditional chemotherapy, is very exciting.”
Dr Áine McCarthy, science information officer at Cancer Research UK, said: “Identifying weaknesses in acute myeloid leukaemia cells is the key to developing much needed new treatments for the disease – and to helping more people survive. This exciting new research has found a new way to target this disease and we look forward to seeing how this could help patients in the future.”
For further information, please contact Henry Winter at the Bloodwise Press Office on 020 7269 9019, press mobile 07824 375880, or email: email@example.com
Notes to Editors
The findings will be published online in Cancer Cell on 11 January 2016 under the title ‘Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia’. Corresponding author: Professor Eric So, Department of Haematological Medicine, King’s College London
Bloodwise is the UK’s biggest blood cancer charity dedicated to improving the lives of patients. The charity, which was formed in 1960, changed its name from Leukaemia & Lymphoma Research in September 2015. The charity’s research is targeted at understanding more about blood cancer, finding causes, improving diagnosis and treatments, and running groundbreaking clinical trials for patients. The charity champions patients’ needs by influencing relevant decision makers and influencers, and seeking to raise awareness of the issues faced by patients. Their patient services provide information, support and assistance to patients at every stage of their journey.
Around 38,000 people of all ages, from children to adults, are diagnosed with blood cancers and related disorders every year in the UK. It is a complex disease area made up of 137 individual diseases. Some affect thousands of people, such as common forms of leukaemia, lymphoma and myeloma. Others affect only a handful. But together, blood cancers are the fifth most common form of cancer.
For more information visit www.bloodwise.org.uk.
About Cancer Research UK
Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research.
Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
Cancer Research UK receives no government funding for its life-saving research. Every step it makes towards beating cancer relies on every pound donated.
Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last forty years.
Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK’s ambition is to accelerate progress so that 3 in 4 people will survive their cancer for at least 10 years within the next 20 years.
Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
Together with its partners and supporters, Cancer Research UK’s vision is to bring forward the day when all cancers are cured.
For further information about Cancer Research UK’s work or to find out how to support the charity, please call 0300 123 1022 or visit www.cancerresearchuk.org. Follow us on Twitter and Facebook.
About King’s College London
King’s College London is one of the top 20 universities in the world (2015/16 QS World University Rankings) and among the oldest in England. King’s has more than 26,500 students (of whom nearly 10,400 are graduate st udents) from some 150 countries worldwide, and nearly 6,900 staff. The university is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
For more information, please visit King’s in Brief (www.kcl.ac.uk/newsevents/About-Kings.aspx).
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