Singapore, 29 March 2016 – A study led by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has uncovered a new clue that may help fight acute myeloid leukaemia (AML), the most common form of cancer of the blood and bone marrow, and an aggressive type of cancer. The findings open a new door to treating the disease more effectively.

AML usually originates from the bone marrow, where blood cells are produced. It is characterised by an overproduction of impaired white blood cells. The differentiation of immature white blood cell precursors into functional white blood cells is an essential process mediating the body’s immunity. The research team found that an enzyme, GCN5, is able to inactivate a protein called C/EBPα in myeloid precursor cells. This prevents immature myeloid white blood cells from maturing into granulocytes - which make up about 70 per cent of white blood cells in the body. As a result, healthy white blood cells formation is disrupted.

The team, which includes Professor Daniel Tenen, Director of CSI Singapore, Ms Kwok Hui Si, PhD student at the Institute, as well as Dr Deepak Bararia, a former Postdoctoral Fellow at the Institute, discovered that the inactivation of the C/EBP protein is carried out by acetylation, which is a process by which GCN5 adds an acetyl group onto C/EBPα reducing the ability of C/EBPα to bind to DNA and modulating its transcriptional activity in the cell.

The findings of the study were published in the journal Nature Communications on 24 March 2016.

Identification of this molecular pathway provides clues towards targeting the GCN5-mediated acetylation of C/EBPα in the treatment of leukaemia.

Prof Tenen said, “As AML is a fast-growing cancer, timely treatment soon after diagnosis could increase patients’ chances of survival. The current main treatment strategy for AML is cytotoxic chemotherapy. Our research results form the basis of an alternative therapeutic strategy that could potentially reduce remission risks and improve cure rates. Moving forward, the team is looking into designing effective GCN5 inhibitors for therapeutic purposes by studying GCN5 in AML further in depth.”

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About National University of Singapore (NUS)A leading global university centred in Asia, the National University of Singapore (NUS) is Singapore’s flagship university, which offers a global approach to education and research, with a focus on Asian perspectives and expertise.

NUS has 17 faculties and schools across three campuses. Its transformative education includes a broad-based curriculum underscored by multi-disciplinary courses and cross-faculty enrichment. Over 38,000 students from 100 countries enrich the community with their diverse social and cultural perspectives.

NUS has three Research Centres of Excellence (RCE) and 26 university-level research institutes and centres. It is also a partner in Singapore’s fifth RCE. NUS shares a close affiliation with 16 national-level research institutes and centres. Research activities are strategic and robust, and NUS is well-known for its research strengths in engineering, life sciences and biomedicine, social sciences and natural sciences. It also strives to create a supportive and innovative environment to promote creative enterprise within its community.

For more information on NUS, please visit www.nus.edu.sg.

About Cancer Science Institute of SingaporeCSI Singapore is a state-of-the-art university research institute affiliated with, and hosted at the National University of Singapore. It was established in 2008, with a “Research Center of Excellence” grant, one of only five in Singapore, by the National Research Foundation and the Ministry of Education. Professor Daniel G. Tenen, MD, a leader in the field of transcriptional regulation, hematopoiesis, and cancer, was named its founding director.

The institute is an anchor for research expertise in two broad programs; Cancer Biology & Stem Cells, and Experimental Therapeutics; these programs form expansive platforms for CSI Singapore’s focus on key cancer disease cancers in gastric, liver, lung and leukemia which are endemic in Asian populations. CSI Singapore aims to position Singapore as a global-leader in the field of Biomedical Sciences. Its mission: to conduct a multifaceted and coordinated approach to cancer research, extending from basic cancer studies all the way to experimental therapeutics and in so doing improve cancer treatment.

For more information on CSI Singapore, visit www.csi.nus.edu.sg/ws/

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Nature Communications