Modulating Leukemia-Initiating Cell Quiescence to Improve Leukemia Treatment
Abstract
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Quiescent leukemia-initiating cells (LICs) are largely resistant to chemotherapy or targeted therapies. The development of new therapeutic approaches that can target LICs will have a profound impact on our ability to eradicate leukemia. We hypothesized that stimulating quiescent LICs to enter the cell cycle will sensitize them to chemotherapy or radiotherapy and improve leukemia treatment. The objective of this application is to further define the role of necdin in regulating LIC quiescence and self-renewal. We have generated two mouse AML models in Necdin null HSCs. We discovered that necdin is not essential for the initiation and progression of AML. We also performed both in vitro and in vivo LIC assays and found that loss of necdin enhances LIC self-renewal. Defining the functions of necdin in normal and leukemic stem cells will provide innovative clinical strategies that are not only useful for eradicating leukemia-initiating cells but will be applicable to the treatment of other human cancers, as well. Successful completion of these studies would be expected to have a potentially important positive impact on military personnel,veterans and their family members, because an increasing percentage of Gulf War veterans are returning from theater with toxin exposure-related AML.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2015
- Accession Number
- AD1001315
Entities
People
- H. S. Boswell
- Michihiro Kobayashi
- Yan Y Liu
- Yunlong Liu