AsianScientist (Jan. 20, 2015) – A study published in Experimental Hematology has found new interactions between two molecules involved in acute myeloid leukaemia (AML): STAT3 and PRL-3. The findings suggest a new therapeutic target for treatment of the aggressive blood cancer.
AML is characterized by an accumulation of dysfunctional blood cells in the body and is associated with poor survival. Previous research found that the PRL-3 protein is overexpressed in 47 percent of bone marrow samples from AML patients. In addition, cellular levels of a transcription factor known as STAT3 were found to be elevated in about 50 percent of AML cases.
Led by Associate Professor Chng Wee Joo, Deputy Director and Senior Principal Investigator at Cancer Science Institute of Singapore (CSI Singapore) and Director of the National University Cancer Institute, the research team demonstrated the connection between PRL-3 and STAT3 for the first time, showing that the STAT3-PRL-3 regulatory loop contributes to the development of AML.
By analyzing a large number of datasets in the scientific literature, Chng and team created a core STAT3 signature that was significantly enriched in AML cases with high PRL-3 expression.
They discovered that STAT3 binds and promotes the production of PRL-3 in cells. A decrease in STAT3 levels led to a corresponding decrease in the levels of PRL-3 and diminished the malignant properties of leukemic cells.
Chng said, “Earlier studies on PRL-3 have been conducted in other cancers, but only in recent years has attention been turned to the significance of PRL-3 in blood cancer.”
“Previously, the mechanism by which PRL-3 is regulated in AML has also not been fully elucidated. This study reveals a novel connection between these two important oncogenes for the first time, and also shows that the STAT3-PRL-3 regulatory loop contributes to the pathogenesis of AML.”
The team is currently looking into methods to target the STAT3-PRL-3 pathway in AML, which could open up new avenues to treat AML patients with high expression of PRL-3 and offer an attractive anti-leukemia therapeutic strategy.
The article can be found at: Zhou et al. (2014) Phosphatase of Regenerating Liver-3 is Regulated by Signal Transducer and Activator of Transcription 3 in Acute Myeloid Leukemia.
Source: National University of Singapore.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.