Hope in myeloid leukaemia fight

13 April 2016 | Research
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Prof Tenen (right) and Hui Si found that the GCN5 enzyme can inactivate a protein in myeloid precursor cells

Patients suffering from acute myeloid leukaemia (AML), the most common cancer of the blood and bone marrow, may have a better chance of fighting the aggressive disease with the recent discovery by scientists from the Cancer Science Institute of Singapore (CSI Singapore) at NUS.

Characterised by the runaway growth of abnormal white blood cells, AML usually originates from the bone marrow — the production site of blood cells. Immature myeloid (bone marrow) white blood cell precursors differentiate into functional white blood cells, and the process is critical to mediating the body’s immunity.

The researchers found that an enzyme called GCN5 can inactivate a protein called C/EBPα in myeloid precursor cells. The inactivation prevents immature myeloid white blood cells from maturing into granulocytes that make up about 70 per cent of white blood cells in the body. This disruption of healthy white blood cell formation can lead to AML.

The team discovered that the inactivation of the C/EBPα protein occurs by acetylation, a process by which GCN5 adds an acetyl group onto the protein, thus reducing its ability to bind to DNA and modulating its transcriptional activity in the cell.

Members of the breakthrough work, published in Nature Communications on 24 March, included Professor Daniel Tenen, Director of CSI Singapore; Kwok Hui Si, PhD student at the Institute; and Dr Deepak Bararia, a former Postdoctoral Fellow at the Institute.

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.”

The team is looking into designing effective GCN5 inhibitors for therapeutic purposes by the in-depth study of GCN5 in AML, he revealed.

See press release.