Researchers discover new therapeutic target for treatment of acute myeloid leukaemia

January 12, 2015
Figure 1: Patients with high PRL-3 expression harbour higher STAT3 activity. (A) The list of genes in the STAT3 core signature. (B) Comparison of the PRL-3 expression (upper panels) and STAT3 activity (C) between high and low PRL-3 groups in patients with AML.

A study by the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has found new interactions between two molecules involved in acute myeloid leukaemia (AML), STAT3 and PRL-3, which may offer a new therapeutic target for cancer treatment. The scientists discovered that STAT3, a molecule which has the potential to cause cancer, associates with and regulates the levels of PRL-3, a gene which has been implicated in various types of cancers.

The study was published in the December issue of Experimental Hematology, the official publication of the Society for Hematology and Stem Cells, and also highlighted in the journal's editorial due to its significance in the biology and treatment of blood cancer.

Led by Associate Professor Chng Wee Joo, Deputy Director and Senior Principal Investigator at CSI Singapore and Director of the National University Cancer Institute, Singapore, the research team found a connection between PRL-3 and STAT3 for the first time and showed that the STAT3-PRL-3 regulatory loop contributes to the development of AML. They 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 leukaemic cells. The scientists 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 personalised therapy for AML patients.

AML is an aggressive blood characterised by an accumulation of dysfunctional blood cells in the body, and AML diagnosis is often associated with poor survival. The research group was the first to report that the PRL-3 protein is overexpressed in 47 per cent of bone marrow samples from AML patients. In addition, cellular levels of STAT3 were found to be elevated in about 50 per cent of AML cases.

In this study, Assoc Prof Chng and Dr Zhou Jianbiao, who is Research Fellow at CSI Singapore, as well as their team created a core STAT3 signature by analysing a large amount of datasets in the literature. They found that STAT3 core signature was significantly enriched in AML cases with high PRL-3 expression.

Figure 2: Schematic of the interaction between STAT3 and PRL-3 in contributing to the development and progression of AML.

Assoc Prof 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 . 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-leukaemia therapeutic strategy.

Explore further: Researchers discover gene that increases incidence of acute myelogenous leukaemia

More information: "Phosphatase of regenerating liver-3 is regulated by signal transducer and activator of transcription 3 in acute myeloid leukemia." Experimental Hematology, Volume 42, Issue 12, December 2014, Pages 1041–1052.e2 DOI: 10.1016/j.exphem.2014.08.001

Related Stories

Researchers discover gene that increases incidence of acute myelogenous leukaemia

September 22, 2014
A novel study by the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) found that an increase in a gene known as Leo1 affects other genes that are directly implicated in acute ...

Blocking STAT3 could help cancer patients in two ways

October 10, 2014
The STAT transcription factors are involved in the development of many forms of cancer. STAT3 is frequently activated in tumour cells, so drugs targeting STAT3 could be used in cancer therapy. However, STAT3 is also important ...

Weakness of leukaemic stem cells discovered

August 4, 2014
Despite improved therapy, only one out of every two adult patients survive acute myeloid leukaemia (AML). The mean survival time for this disease, which predominantly occurs in the elderly, is less than a year for patients ...

Unexpected synergy between two cancer-linked proteins offers hope for personalised cancer therapy

August 6, 2013
A team of scientists from A*STAR's Institute of Molecular and Cell Biology (IMCB) have discovered a new biomarker which will help physicians predict how well cancer patients respond to cancer drugs. Having the means to identify ...

Genetic errors linked to aging underlie leukemia that develops after cancer treatment

December 8, 2014
For a small percentage of cancer patients, treatment aimed at curing the disease leads to a form of leukemia with a poor prognosis. Conventional thinking goes that chemotherapy and radiation therapy induce a barrage of damaging ...

Oral inhibitor shows clinical activity in poor-prognosis AML

December 8, 2014
An oral targeted drug has shown encouraging activity and tolerable side effects in patients with treatment-resistant or relapsed acute myelogenous leukemia (AML) - a poor-prognosis group with few options - report investigators ...

Recommended for you

Targeted antibiotic use may help cure chronic myeloid leukaemia

September 19, 2017
The antibiotic tigecycline, when used in combination with current treatment, may hold the key to eradicating chronic myeloid leukaemia (CML) cells, according to new research.

Brain powered: Increased physical activity among breast cancer survivors boosts cognition

September 19, 2017
It is estimated that up to 75 percent of breast cancer survivors experience problems with cognitive difficulties following treatments, perhaps lasting years. Currently, few science-based options are available to help. In ...

Researchers compose guidelines for handling CAR T cell side effects

September 19, 2017
Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University ...

Bone marrow protein a 'magnet' for passing prostate cancer cells

September 19, 2017
Scientists at the University of York have shown that a protein in the bone marrow acts like a 'magnetic docking station' for prostate cancer cells, helping them grow and spread outside of the prostate.

Brain cancer breakthrough could provide better treatment

September 19, 2017
A new discovery about the most common type of childhood brain cancer could transform treatment for young patients by enabling doctors to give the most effective therapies.

A new paradigm for treating transcription factor-driven cancers

September 18, 2017
In the current issue of Proceedings of the National Academy of Sciences, researchers from Nationwide Children's Hospital describe a new paradigm for treating transcription factor-driven cancers. The study focuses on Ewing ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.