A molecular mechanism in blood cells may offer a new drug target for acute myeloid leukaemia (AML).
The team - from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) - reports the findings in the journal Experimental Hematology.
Acute myeloid leukemia (AML) is an aggressive blood cancer whose diagnosis is often associated with poor survival. The cancer starts in cells that would normally develop into various types of blood cell.
As AML progresses, more and more dysfunctional blood cells accumulate in the body.
The disease mostly affects older people and is not usually seen in patients under the age of 45.
According to the American Cancer Society, there were about 18,860 new cases of AML and 10,460 deaths to the disease in the US in 2014.
PRL-3 and STAT3 form a regulatory loop that contributes to development of AML
The two molecules identified in the new study - which have been associated with AML before - are the transcription factor STAT3 and the gene PRL-3. A transcription factor is a protein that switches genes on and off by binding to DNA and other proteins.
The Singapore team was the first to report that PRL-3 is overexpressed in 47% of patients with AML. The authors note that higher cellular levels of STAT3 are also found in around 50% of cases of AML.
However, their new study is the first to show the two molecules form a regulatory loop that contributes to the development of AML.
Lead investigator Chng Wee Joo, associate professor at the NUS Yong Loo Lin School of Medicine and deputy director of CSI Singapore, says:
"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."
Disruption of STAT3-PRL-3 regulatory loop could be a promising treatment for AML
For their study, the researchers created a core signature for STAT3 by analyzing large datasets in the literature. Using this core signature, they established that STAT3 was significantly enriched in AML patients with high PRL-3 expression.
Using mouse and human cells, they found that STAT3 binds to and promotes the production of PRL-3 in cells, and reducing levels of STAT3 lowered PRL-3 levels and diminished the malignancy of leukemic cells.
They conclude that disruption of this regulatory loop may be a promising way to treat AML and that PRL-3 could be a possible biomarker in personalized therapy for AML patients.
The team is now looking for ways to target the pathway in AML.
In April 2014, Medical News Today also learned about the idea that a gene within a gene drives acute myeloid leukemia. In a study published in Science Signaling, researchers from the US describe how they found it is a smaller gene embedded inside a larger gene already linked to poor survival of AML patients that actually drives progression of the disease.