Targeting Leukemia-Initiating Cells to Improve Leukemia Treatment

Pediatric leukemias account for almost 35 percent of all childhood cancers, leaving leukemia as the leading cause of cancer death for children. In addition to children, leukemia also affects adults. Adult leukemia usually occurs around age 60 and carries a very poor prognosis, with most patients live less than 18 months. Leukemia is initiated and maintained by a rare population of leukemia-initiating cells (LICs). LICs, and in particular those that are in a dormant state, are resistant to chemotherapy or targeted therapies. As we found that protein tyrosine phosphatase PRL2 is highly expressed in MLL leukemias, the objective of this proposal is to determine the effects of genetic and pharmacological inhibition of PRL2 on human leukemia-initiating cells in order to further assess its clinical potential. We found that PRL2 is essential for the self-renewal and survival of LICs expressing MLL-AF9. We developed a novel PRL2-specific inhibitor (PRLi) and found that PRLi treatment decreases the proliferation and survival of human MLL leukemia cells in vitro. Importantly, we found that in vivo PRLi treatment significantly increases the survival of MLL leukemia mice. The proposed work will facilitate the clinical application of PRL2 inhibitors intreating military personnel, veterans and their dependents with leukemia, thus improving their quality of life.