Genetics Of Leukemia Decoded

Singapore researchers discover a gene that increases incidence of acute myelogenous leukaemia, providing an avenue for targeted therapy to treat the disease.

AsianScientist (Oct. 3, 2014) – A study has found that an increase in a gene known as Leo1 affects other genes that are directly implicated in acute myeloid leukemia (AML), leading to a subsequent increase in cancer incidence. The findings have been published in Cancer Research, the official journal of the American Association of Cancer Research.

AML, a cancer of the myeloid line of blood cells, is the most common acute leukemia affecting adults. It is characterized by the abnormal, rapid growth of white blood cells in the bone marrow, which then disrupt the development of normal blood cells

The researchers, led by Associate Professor Chng Wee Joo, of the National University of Singapore’s Cancer Science Institute of Singapore, found that Leo1’s involvement in cancer development is related to its regulatory activities over the protein PRL-3.

Results also showed that PRL-3 plays a role in the regulation of ribonucleic acid related processes, advancing current understanding of how the protein contributes to cancer progression.

The elevated expression of PRL-3 has previously been implicated in the progression and metastasis of an array of cancer types, including gastric, ovarian, cervical, lung, liver, and breast. In particular, the protein is over-expressed in about half of AML patients and associated with poor survival.

Prof. Chng’s team were the first to report that elevated PRL-3 protein expression occurs in almost 50 percent of AML cases, while being absent from normal myeloid cells in bone marrow. PRL-3 could thus be used as a therapeutic target without concerns of damaging normal blood cell tissue.

For the next phase of research, the team is validating several important proteins directly downstream of Leo1 that could possibly be used as biomarkers and drug targets to improve treatment for leukemia with PRL-3 overexpression.

“Our previous studies showed that PRL-3 is clinical and biologically important in AML, and may therefore be a useful treatment target. In the current study, we have taken the work further by understanding how PRL-3 confers cancer properties to the leukemia cells,” said Prof. Chng.

“This now provides a framework for rational design of a treatment based on mechanistic understanding. In the process, we will also develop biomarkers to better select patients for the treatment and hence, progress towards personalizing treatment for leukemia patients.”

The article can be found at: Chong et al. (2014) LEO1 Is Regulated by PRL-3 and Mediates Its Oncogenic Properties in Acute Myelogenous Leukemia.


Source: National University of Singapore; Photo: Yale Rosen/Flickr/CC
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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