Scientists have identified a connections between two molecules may lead to the development of acute myeloid leukemia. They suggest the pathway could be a probable target for dealing with the aggressive blood cancer and that one of the molecules could function as a biomarker in personalized therapy of the disease.
The team of researchers from the Cancer Science Institute of Singapore published the results in the journal Experimental Hematology.
Acute myeloid leukemia (AML) is an aggressive blood cancer whose diagnosis is usually connected with inadequate survival. The cancer begins in cells that would generally develop into different kinds of blood cell.
As AML advances, more and more dysfunctional blood cells build up in the body.
The disease generally impacts older people and is not generally observed in sufferers below the age of 45.
With respect to the American Cancer Society, there were around 18,850 new cases of AML and 10,450 deaths due to the condition in the US in 2014.
PRL-3 and STAT3 form a regulatory loop that leads to development of AML
The two molecules determined in the new research – which have been connected with AML before – are the transcription factor STAT3 and the gene PRL-3. A transcription factor is a protein that modifies genes on and off by holding to DNA and other proteins.
The Singapore group was the initial to report that PRL-3 is over-expressed in 47% of sufferers with AML. The authors note that greater cellular levels of STAT3 are also identified in about half of cases of AML.
However, their new investigation is the initial to show the two molecules form a regulatory loop that leads to the growth of AML.
Led researcher Chng Wee Joo, states that:
“Previous research on PRL-3 has been performed in other cancers, but only in latest years has focus been turned to the importance of PRL-3 in blood cancer. Earlier, the mechanism by which PRL-3 is managed in AML has also not been completely elucidated.”
Interruption of STAT3-PRL-3 regulatory loop could be an ensuring therapy for AML
For their research, the scientists designed a core signature for STAT3 by examining huge datasets in the literature. Making use of this key signature, they build that STAT3 was significantly rich in AML sufferers with high PRL-3 expression.
Using mouse and human cells, they identified that STAT3 binds to and encourages the production of PRL-3 in cells, and decreasing levels of STAT3 reduced PRL-3 levels and diminished the malignancy of leukemic cells.
They conclude that interruption of this regulatory loop may be a ensuring way to deal with AML and that PRL-3 could be a probable biomarker in personalized treatment for AML sufferers.
The group is now searching for approaches to focus on the pathway in AML.