A research team led by Nanyang Technological University (NTU) scientists have made a key finding which is expected to open up improved treatment possibilities for children suffering from leukaemia.
They found that two in three cases of acute lymphoblastic leukaemia, a type of cancer of the white blood cells, may be caused by mutations in one of the two key genes found in children. These genes are however more prevalent in those with Down syndrome.
This means that scientists can design better tailored treatment protocols, depending on which mutating gene is carried by the patient. Such treatments may include lower doses of anti-cancer drugs thus leading to fewer side effects.
Acute lymphoblastic leukaemia is the most common cancer in children, with 50 to 100 children diagnosed each year in Singapore. This gene discovery is good news for those with Down syndrome and the 20 per cent of children who do not respond well to standard therapy.
Children with Down syndrome have a 20 to 50 fold greater risk of developing this blood cancer. They are also prone to suffer a relapse and have a higher risk of dying from the side effects of therapy.
The discovery, made by an international team led by Professor Dean Nizetic from NTU's Lee Kong Chian School of Medicine, was published in the prestigious academic journal Nature Communications last week.
Prof Nizetic's team of experts in ageing and Down syndrome collaborated with researchers from the Queen Mary University in London and the universities of Geneva and Padua on this study.
"By analysing the DNA sequence of patient samples at different stages of the disease, we identified mutations in two genes that turn normal blood cells into cancer cells," said Prof Nizetic, the senior author of the study.
The research team found that the two genes (RAS and JAK) never mutate together, which makes them ideal biomarkers.
"This could benefit all children affected by the disease as clinicians would be able to offer tailored, more specific and less toxic treatments, reducing side effects and even cutting down the number of side effect-related deaths," added Prof Nizetic.
Prof Nizetic's team at LKCMedicine is focusing on Down syndrome to gain a better understanding of the condition, which presents many complex mysteries. In people with Down syndrome, their cells show signs of accelerated ageing and accumulated DNA damage. Paradoxically, they seem to be protected from most common solid tissue cancers in adulthood.
"Some people with Down syndrome appear protected from ageing-related diseases, such as dementia, atherosclerosis and Type II diabetes despite increased risk factors," said Prof Nizetic.
"Studying cells from people with Down syndrome could not only help them lead longer, and healthier lives, but also provide important clues in understanding the general mechanisms of ageing, Alzheimer's dementia, cancer, atherosclerosis, diabetes, and a number of other common conditions, and this has so far not been sufficiently explored."
Moving forward, the NTU research team will be conducting more studies on the findings of the two key genes. This is to see how else they might affect both normal children and children with Down syndrome, who are suffering from this form of leukaemia.
Down Syndrome Association (Singapore) welcomes discovery
Dr Balbir Singh, Advisor and Founding Chairman, Down Syndrome Association (Singapore), hopes that these findings will lead to "a better, less toxic treatment for all children affected by this disease" and welcomed the new research interest in Down syndrome.
"Associations and organisations of parents and carers for people with Down syndrome are very interested in participating in any research that could increase prospects of improving their health, quality of life and inclusion into society," Dr Singh said.
"It makes people with Down syndrome twice as proud, and feel both important and included, if studying them could help in better understanding and fighting the diseases, such as Alzheimer's, stroke, heart attack and cancer, for all people. The Down Syndrome Association (Singapore) welcomes more research in this direction."
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About Nanyang Technological University
A research-intensive public university, Nanyang Technological University (NTU) has 33,500 undergraduate and postgraduate students in the colleges of Engineering, Business, Science, Humanities, Arts, & Social Sciences, and its Interdisciplinary Graduate School. It has a new medical school, the Lee Kong Chian School of Medicine, set up jointly with Imperial College London.
NTU is also home to world-class autonomous institutes – the National Institute of Education, S Rajaratnam School of International Studies, Earth Observatory of Singapore, and Singapore Centre on Environmental Life Sciences Engineering – and various leading research centres such as the Nanyang Environment & Water Research Institute (NEWRI), Energy Research Institute @ NTU (ERI@N) and the Institute on Asian Consumer Insight (ACI).
A fast-growing university with an international outlook, NTU is putting its global stamp on Five Peaks of Excellence: Sustainable Earth, Future Healthcare, New Media, New Silk Road, and Innovation Asia.
Besides the main Yunnan Garden campus, NTU also has a satellite campus in Singapore's science and tech hub, one-north, and a third campus in Novena, Singapore's medical district.
For more information, visit http://www.ntu.edu.sg
About Lee Kong Chian School of Medicine
The Lee Kong Chian School of Medicine, a partnership between Nanyang Technological University (NTU) and Imperial College London, will train a generation of doctors who will put patients at the centre of their exemplary medical care. Graduates of the five-year undergraduate medical degree programme, which matriculated its inaugural cohort in 2013, will have a strong understanding of the scientific basis of medicine, along with interdisciplinary subjects including business management, humanities and technology.
The School's primary clinical partner is the National Healthcare Group, a leader in public healthcare recognised for the quality of its medical expertise, facilities and teaching. The School, named after local philanthropist Tan Sri Dato Lee Kong Chian, aims to be a future model for innovative medical education. Its first doctors will graduate in 2018 with a Bachelor of Medicine and Bachelor of Surgery (MBBS), awarded jointly by NTU and Imperial College London, and become doctors who will enhance Singapore's healthcare in the decades to come.
For more information, visit http://www.lkcmedicine.ntu.edu.sg
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