Targeting Super-Enhancers To Fight Leukemia

The protein TAL1 activates a ‘molecular switch’ that triggers a cluster of genes leading to the cancerous growth of T-cell precursors.

AsianScientist (Jun. 1, 2017) – Researchers from the National University of Singapore (NUS) have identified a ‘super-enhancer’ region of the human genome that is activated in patients with T-cell acute lymphoblastic leukemia (T-ALL). Their findings have been published in Leukemia.

“Currently, most of the patients with T-ALL are young children. While recent improvements in chemotherapy have significantly boosted cure rates for T-ALL, the introduction of intensive chemotherapy causes both short- and long-term adverse effects. Moreover, there are only a limited number of new drugs with specific activity against malignant T-cells,” said study leader Assistant Professor Takaomi Sanda, a principal investigator at the Cancer Science Institute of Singapore.

Noting that the oncogene TAL1 is highly prevalent in patients with T-ALL, Sanda and his team sought to identify the genes activated by TAL1. They found that TAL1 turns on a ‘molecular switch’ called a super-enhancer, which subsequently activates a cluster of genes called GIMAP. This in turn results in the abnormal growth of T-cell precursors, leading to the development of T-ALL.

“Moving forward, we are looking into identifying potential therapeutic compounds that inhibit the activation of this super-enhancer. We hope to be able to translate it into meaningful therapies for patients afflicted by T-ALL,” Sanda said.

The article can be found at: Liau et al. (2016) Aberrant Activation of the GIMAP Enhancer by Oncogenic Transcription Factors in T-cell Acute Lymphoblastic Leukemia.


Source: National University of Singapore; Photo: Shutterstock.
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