Rescue Hematopoietic Stem and Progenitor Cell Functions in Bone Marrow Failure Syndromes
Abstract
Fanconi anemia (FA) is one of the most common inherited bone marrow failure syndromes. Although initially identified over 85 years ago, FA remains a fatal genetic disease. If left untreated, 90% of children experience severe bone marrow failure or leukemia. There are few therapeutic options besides stem cell transplant (SCT), but the latter is associated with high risks of morbidity and mortality. Despite greater survival of children into adulthood as a result of SCT, the specter of the potential for solid tumors remains a serious problem. The defects underlying this disease spectrum impair the ability of affected individuals to repair damage to their genetic material as it occurs naturally or through exposure to environmental toxins. The failure to appropriately deal with damaged genes especially hurts one type of cells in the body, called blood stem cells that are located in the bone marrow. These stem cells normally replenish blood supply for a lifetime, but in the case of FA undergo attrition and finally complete exhaustion, leading to a condition called bone marrow failure. Our work offers a new strategy by which the stem cell defect in FA might be overcome. Specifically, we discovered a gene, called LNK, which when disrupted leads to the expansion of blood stem cells in animal models including normal and FA animals. We plan to follow up on what we believe to be a remarkable result by trying to better understand the mechanisms by which LNK functions in normal and FA blood stem cells and devising means to perturb LNK as a novel approach to treat this devastating group of diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710079
Entities
People
- Wei Tong
Organizations
- United States Army