Researchers at Pusan National University found that suppressing SURF4 expression reduces pathological processes that contribute to leukemia progression. Credit: Professor Dongjun Lee, Pusan National University
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, reducing the number 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 – surfeit 4 (SURF4) – is highly expressed in leukemia 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, Republic of Korea, set out to understand this. They were led by professors Dongjun Lee and Yun Hak Kim, who explain the rather humanitarian motive behind their research.
“Children who suffer relapse of AML rarely survive. This makes studying the mechanisms of AML very important. Discovering the effects of proteins like SURF4 may lead to new therapeutic strategies for AML, which has not happened in four decades,” the team reports. 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, using multiple short hairpin RNA constructs to target SURF4, 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 SURF4 expression levels among AML patients and saw that patients with higher SURF4 expression levels had significantly shorter survival. It was also observed that the expression of SURF4 was much higher in patients suffering from AML compared to healthy people. These observations suggest that SURF4 regulates cell death and differentiation in AML. Interestingly, SURF4 silencing did not affect cell cycle status.
“Our research shows the role that SURF4 plays in myeloid leukemia. It negatively regulates the STING-TBK1-STAT6 axis and inhibits the death of cancer cells. We also discovered that the reduction of SURF4 works synergistically with anticancer drugs to reduce the burden of myeloid leukemia cells,” says Prof. Lee.
“Therefore,” concludes prof. Kim, “inhibition of SURF4 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 hematologic cancers.”
More information:
Jayoung Kim et al, A Novel Endogenous Endoplasmic Reticulum Transmembrane Protein SURF4 Suppresses Cell Death by Negatively Regulating the STING-STAT6 Axis in Myeloid Leukemia, Cancer Communications (2022). DOI: 10.1002/cac2.12390
Facilitated by Pusan National University
Quote: Researchers discover new gene that regulates leukemia development and progression (2023, January 31) Retrieved January 31, 2023 from https://medicalxpress.com/news/2023-01-uncover-gene-leukemia.html
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