Study finds new treatment target for aggressive blood cancer

Date: Jan-13-2015 Researchers have discovered an interaction between two molecules may contribute to the development of acute myeloid leukemia.

They suggest the pathway could be a potential target for treating the aggressive blood cancer and that one of the molecules could serve

as a biomarker in personalized therapy of the disease.

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.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.