The Role of Mitochondria in Bone Marrow Failure
Abstract
Bone marrow failure syndromes (BMFS) include a group of disorders that can be either inherited or acquired. The inherited bone marrow failure syndromes (IBMFS) include genetic disorders. The acquired bone marrow failures include aplastic anemia (AA) and myelodysplastic syndromes (MDS). In these disorders, the hematopoietic stem cell (HSC) compartment, which normally produces to all blood cells, is impaired and is unable to generate blood cells (red cells, leukocytes, and platelets) in sufficient amount. Therefore, patients with such disorders suffer from fatal infections, excessive bleeding, and anemia. Abnormal immune reactions that “kill” HSCs are a common cause of BMFS. In addition, in these patients, the normal regulation of HSCs is impaired, preventing them to generate blood cells. The anomalies in the regulation of HSC in BMFS is an important cause of BMF; yet, it has been poorly characterized. This lack of knowledge about BMFS significantly hampers the development of relevant experimental animal models of the disease and of therapies for BMFS. This grant is designed to understand the role of molecules whose functioning is abnormal in HSC, thereby causing BMFS. The novelty of our proposal lies in the investigation of a molecule previously not recognized, namely TGF-beta together with viral inflammation-induced molecules, whose expression is abnormally high in BMFS patients, and may be a cause of abnormal functioning of HSC. It is clinically important, because the activity of this molecule could be directly targeted by pharmacological drugs. Drug targeting this molecules have already been approved by the FDA, which would greatly facilitate its development for the indication of BMFS. Hence, our work may not only lead to the development of a novel animal model of BMF; it will also provide the foundation for novel therapeutic approach of BMFS.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010689
Entities
People
- Marie-dominique Filippi
Organizations
- United States Army