According to genetic research, the answer lies in dynamic shifts in a person’s genotype that ultimately drive clinical phenotypic changes. “Mutated hematopoietic cells begin to pick up more mutations that give them a clonal selective advantage,” says Dr Michael Savona, Director of Hematologic Malignancies Research and Early Therapy Program at Vanderbilt University Medical Center and founder of CHIVE (Clonal Hematopoiesis and Inflammation in the VasculaturE), a multidisciplinary group at Vanderbilt studying aging-related clonal hematopoiesis of indeterminate potential (CHIP).
As mutated cells pick up more mutations, the disease progresses, says Dr Savona. “When the mutations lead to a dysregulation in how genes are spliced, or an overproliferation or an epigenetic signal that disrupts how genes are transcribed, it changes the balance of the pro- and anti-inflammatory signaling within the bone marrow.” In turn, when bone marrow gets “out of whack,” says Dr Savona, proteins like danger associated molecular patterns (DAMPs) and toll-like receptors (TLR) change immune signaling in the bone marrow, further propagating an inflammatory signal and increasing the risk of developing more mutants.
Choose a Story
