Targeting Leukemia-Initiating Cells to Improve Leukemia Treatment
Abstract
As of September 2018, 1,429,995 people were on active duty in the United States military, with an additional 848,000 people in the seven reserve components. The number of military Veterans in the United States in 2014 is 21.8 million. Active duty military members are frequently exposed to ionizing irradiation, chemicals, infectious agents and/or environmental carcinogens. This exposure can cause mutations in blood cells that lead to blood cancers (leukemias). For instance, there are increasing numbers of Gulf War Veterans returning from theater with irradiation or toxin exposure-related leukemia. Adult leukemia usually occurs around age 60 and carries a very poor prognosis, with most patients living less than 18 months from initial diagnosis. In addition to adults, childhood leukemia accounts for almost 35% of all childhood cancers, leaving leukemia as the leading cause of cancer death for children. There are currently 8 to 10 million military dependents in the United States. Together, approximately 2,000 military personnel, Veterans and their dependents are expected to develop acute leukemia in the United States in 2018. Thus, there is an urgent need to develop new drugs that are effective for leukemia patients. The initial treatment of leukemia is designed to achieve a complete remission; however, leukemia relapse occurs because current chemotherapies fail to eliminate dormant leukemia initiating cells (LICs) in the blood after remission. Leukemia initiating cells (LICs) particularly those that are in a dormant state and capable of self-renewal are resistant to chemotherapy and targeted therapies. We found a protein called PRL2 is highly expressed in human leukemia cells. We demonstrated that PRL2 is important for the self-renewal and survival of leukemia-initiating cells. We developed an inhibitor for PRL2 and found that inhibiting PRL2 activity decreases the proliferation and survival of leukemia cells. We believe that inhibiting PRL2 will eliminate drug resistant leukemia-initiating cells, improving leukemia treatment. Upon completion of this research, we expect to establish PRL2 as a new druggable target for clinical trials, thereby providing new drugs for childhood and adult leukemia patients. The successful completion of these studies would be expected to have an important positive impact on military personnel, Veterans, and their family members. In addition, the proposed work will facilitate the clinical application of PRL2 inhibitors in treating military personnel, Veterans, and their dependents with leukemia, thus improving their quality of life.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910575
Entities
People
- Yan Y Liu
Organizations
- Indiana University – Purdue University Indianapolis
- United States Army