Credit: Lance Liotta
Researchers have discovered that interactions between two molecules—STAT3 and PRL-3—may provide a therapeutic target for acute myeloid leukemia (AML).
The team found evidence to suggest that the STAT3-PRL-3 regulatory loop contributes to the development of AML.
Chng Wee Joo, MB ChB, PhD, of the National University Cancer Institute in Singapore, and his colleagues reported these findings in Experimental Hematology.
The researchers discovered that STAT3, a transcription factor, 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.
The team therefore concluded that a disruption of this regulatory loop may offer an attractive anti-AML therapeutic strategy. Furthermore, PRL-3 has the potential to be used as a biomarker in personalized therapy for AML patients.
The group was the first to report that the PRL-3 protein is overexpressed in 47% of bone marrow samples from AML patients. In addition, cellular levels of STAT3 were found to be elevated in about 50% of AML cases.
The researchers created a core STAT3 signature by analyzing datasets in the scientific literature. And they found that STAT3 core signature was significantly enriched in AML cases with high PRL-3 expression.
“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,” Dr Chng said.
“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 researchers are now 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.
