NUS researchers uncover the new role of RNA editing enzyme in acute myeloid leukaemia

Blood cancers are the fifth most common type of cancer globally, with around 1.3 billion new cases of blood cancer diagnosed in 2020 alone. Acute myeloid leukemia (AML), which is a cancer of the blood and bone marrow, is the most common type of acute leukaemia in adults. Core binding factor-acute myeloid leukaemia (CBF-AML) is a type of blood cancer and accounts for up to 20 percent of all cases of AML.

In a recently published study, researchers from the Cancer Science Institute of Singapore (CSI Singapore) at NUS demonstrated for the first time the mechanism that causes the suppression of the RNA editing enzyme known as adenosine deaminases acting on RNA (ADAR2). The NUS researchers also show how understanding this mechanism can explain the development of CBF-AML.

The study was co-led by Professor Daniel G. Tenen and Associate Professor Polly Chen Leilei, and the results were published in the prestigious journal Blood on 16 February 2023.

Multiple cancers are known to develop due to the dysregulation of RNA editing capabilities of the ADAR family of enzymes. However, its role in blood cancers remains unclear, particularly in CBF-AML. Therefore, the NUS research team set out to prove their hypothesis that the suppression of ADAR2 and its RNA editing properties could contribute to the development of CBF-AML.

In their study, the researchers activated ADAR2 in CBF-AML and non-CBF-AML cells. They found that the RNA editing capability of ADAR2 was necessary to suppress the development of leukaemia in CBF-AML cells.

Assoc Prof Chen, the co-lead author of this research, said, “The understanding of the role of ADAR2 and ADAR2-mediated RNA editing in cancer has long been neglected, with researchers in this field being more focused on the role of ADAR1 and RNA editing in cancers, including haematological malignancies. Our motivation is to systematically investigate the potential role of ADAR-mediated RNA editing in AML.”

This study is the first to map out the importance of RNA editing properties of ADAR2 in preventing the development of CBF-AML, and it is a significant first step towards the future development of RNA therapeutics against CBF-AML for better patient treatment outcomes.

Following this study, the NUS team will further examine the causes and functional consequences of suppressing ADAR2 in other diseases, including cancer, to identify the processes that can lead to the development of the disease.

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