Pusan ​​National University researchers discovered a new gene that regulates the development and progression of leukemia

The findings of this study could lead to a new therapeutic strategy for acute myeloid leukemia for the first time in four decades

BUSAN, South Korea, February 1, 2023 /PRNewswire/ — Leukemia, a type of blood cancer, affected an estimated 2.3 million people worldwide in 2015. Acute myeloid leukemia (AML)—a particularly aggressive disease—generally begins in the bone marrow, when stem cells cannot differentiate into white blood cells. cells, which reduces the number of healthy blood cells in the body, leading to a very weak immune system, among other problems. Given the prevalence and implications of this disease, there has been much research into the development and progression of leukemia. This led to the discovery of a protein, stimulator of the interferon gene (STING), which interacts with two other proteins—TANK-binding kinase 1 (TBK1) and signal transducer and activator of transcription 6 (STAT6)—to exert anticancer effects in blood cancer. The researchers also noticed that a particular gene—surplus 4 (SURFING4)—is highly expressed in leukemic cells, and its protein, SURF4, binds to STING. However, we still do not understand how SURF4 affects the STING-TBK1-STAT6 axis and what role it plays in leukemia. So, a team of researchers from Pusan National University, the Republic of Korea sought to understand this. They were led by prof Dongjun Lee and Yun Hak Kimwhich explain the rather humanitarian motive of their research. “Children who suffer from relapse of AML rarely survive. This makes studying the mechanisms of AML very important. Discovering the effects of proteins like SURF4 can lead to new therapeutic strategies for AML, which has not happened in four decades.” The team conducted a series of experiments, the findings of which are detailed in a letter to the editor, published on November 6, 2022 in Cancer Communications.

First, the use of multiple short hairpin RNA constructs for targeting SURFING4, the team suppressed its expression in myeloid leukemia cells and compared them to control leukemia cells. The former showed increased cell differentiation, cell death and ROS accumulation. Tumors containing these cells also show arrested growth when inoculated into mice. The researchers further compared SURFING4 expression levels among patients with AML and saw that patients with higher SURFING4 expression levels had significantly shorter survival. It was also observed that SURFING4 expression was much higher in AML patients compared to healthy people. These observations suggest that SURFING4 regulates cell death and differentiation in AML. interestingly, SURFING4 silencing did not affect cell cycle status.

Our research shows the role of SURF4 in myeloid leukemia. It negatively regulates the STING-TBK1-STAT6 axis and inhibits cancer cell death. We also found that SURF4 depletion works synergistically with anticancer drugs to reduce myeloid leukemia cell burden,” says prof. Lee.

Therefore,” Prof. Kim concludes, “inhibiting SURFING4 expression using monoclonal antibodies and/or aptamers may represent a better alternative to current cancer therapies that destroy the immune system and have multiple side effects. This is a promising option for the treatment of hematological cancers.”

Overall, their discoveries have increased our understanding of AML and opened new avenues for the treatment of not only AML but also other types of blood cancer.


Title of the original paper: A novel endogenous endoplasmic reticulum transmembrane protein SURF4 suppresses cell death through negative regulation of the STING-STAT6 axis in myeloid leukemia

Magazine: Cancer Communications

DOI: https://doi.org/10.1002/cac2.12390

*E-mail of the author for correspondence:
Dongjun Lee: [email protected]
Yun Hak Kim: [email protected]

Eye Pusan National University
Website: https://www.pusan.ac.kr/eng/Main.do

Jae-Eun Lee
82 51 510 7928
[email protected]



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SOURCE Pusan National University

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