Regulators of Clonal Hematopoiesis and Physiological Consequences of this Condition

Park, Eunbee, Biochemistry and Molecular Genetics - School of Medicine, University of Virginia
Walsh, Kenneth, MD-INMD CV Medicine, University of Virginia

Clonal hematopoiesis of indeterminate potential (CHIP) is a newly identified phenomenon associated with aging that has significant implications for overall health. It is characterized by the presence of certain cancer-related somatic mutations in blood cells, even in the absence of any blood cancer or other abnormal clonal conditions. These mutations are believed to provide a competitive advantage to hematopoietic stem cells (HSCs), enabling them to expand as a clone while still undergoing normal blood cell production. Extensive efforts have been directed towards comprehending the connection between CHIP and various diseases. However, there has been comparatively less emphasis on investigating the regulating factors that contribute to the formation and expansion of the CHIP clone. This thesis aims to address this gap and specifically examine the relationship between these regulatory factors and CHIP development and yielded valuable insights into the factors that contribute to the proliferation of mutant clones in CHIP and the resultant consequences associated with this phenomenon. Our research findings indicate that irradiation serves as a positive regulatory factor in the expansion of CHIP clone, while inflammation induced by colitis does not exert a significant influence. Furthermore, our results demonstrate that the severity of viral diseases is not correlated with the presence of CHIP clone. These findings contribute to our understanding of the impact of regulatory factors on the development of CHIP and have significant implications for mechanistic investigations and potential therapeutic interventions for individuals affected by CHIP.

PHD (Doctor of Philosophy)
clonal hematopoiesis, inflammation, radiation, clone expansion
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