The role of bone marrow inflammation in the progression of clonal hematopoiesis to blood cancers

Project: Research project

Description

FY18 PRCRP Topic Area to be addressed: Blood cancers.
Scientific objective and rationale: Blood cancers are originated from the bone marrow and commonly seen in ageing patients. There are many possible etiologies related to different types of blood cancers but why ageing is associated with an increased incidence of blood cancers is unclear. Recent advances in biomedical research reveal that certain old individuals (10-20% of the population over age 70), who are apparently healthy, carry gene mutations in their blood cells that lead them to have an increased risk to develop blood cancers. However, how these age-related mutations promote blood cancer development is unclear. In this respect, several reports including ours demonstrate that an age-related inflammatory bone marrow environment is also critical for the initiation of blood cancers. The objective of our project is to use our recently developed animal models to investigate how mutations cooperate with the inflammatory bone marrow environment to induce blood cancer development and disease progression.
Ultimate applicability of the research: Our research will help explain how age-related bone marrow environment and mutations in the blood cells cooperate to induce blood cancer development. This will benefit ageing “healthy” individuals with detectable mutations in their blood cells, or ageing blood cancer patients with inflammation. Frequently, mutations and inflammation coexist in ageing individuals. Successful completion of our project will benefit these individuals through the treatment of inflammation. Our project will also make it possible to open a new direction for the development of novel immunotherapeutic targets for the management of these individuals.
FY18 PRCRP Military Relevance Focus Area to be addressed: Our project addresses militarily relevant risk factors associated with blood cancers. As mentioned above, mutations in blood cells and inflammation are common in general old population. However, inflammation and inflammatory bone marrow environment are particularly important and disproportionately relevant in the military setting due to the increased likelihood of inflammation in active duty service members and veterans when compared to general population. Because the active duty service members and veterans have an increased chance of exposure to infection and radiation, which are potent inducers of inflammation.
StatusActive
Effective start/end date9/1/198/31/21

Funding

  • U.S. Army Medical Research and Materiel Command (W81XWH1910228)

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Osteitis
Hematopoiesis
Bone Marrow
Inflammation
Neoplasms
Mutation
Blood Cells
Veterans
Population
Bone Neoplasms
Cell Aging
Research
Disease Progression
Biomedical Research
Animal Models