Scientists from National University of Singapore have found the overexpression of Leo1 gene will significantly influence other genes which have directly relations with Acute Myelogenous leukemia(AML), then enhance the incidence of cancer. Through inhibiting Leo1 and its downstream signaling pathway, this study, published in Cancer Research, potentially provides a new regimen for AML patients.

PRL-3 is a small dual specificity phosphatase and has been shown to promote cellular processes, such as cell motility, invasion and survival. PRL-3 was first linked to cancer when it was consistently found at elevated levels in colorectal cancer metastases, but at much lower levels in matched early-staged tumor and normal colorectal epithelium. Stable expression of PRL-3 confers cytokine independence and growth advantage of AML. However, how PRL-3 mediates these functions in AML is still unknown.

In this study, researchers have indicated that Leo1, a component of RNA polymerase -associated factor(PAE) complex, is a novel and important mediator of PRL-3 oncogenic activities in AML. They have described a novel mechanism where elevated PRL-3 protein increases JMJD2C histone demethylase occupancy on Leo1 promoter, thereby reducing the H3K9me3 repressive signals and promoting Leo1 gene expression. Inhibition of Leo1 reverses PRL-3 oncogenic phenotypes in AML. Loss of Leo1 leads to destabilization of PAF complex and downregulation of SOX2 and SOX4, potent oncogenes in myeloid transformation.

This finding has implicated a pro-oncogenic role of PRL-3 in AML, and reveals Leo1 as a novel downstream molecule required for PRL-3 oncogenic function in leukemia.