ABC Heart Fail Cardiomyop 2022; 2(2): 218-221
The Impact of Clonal Hematopoiesis of Indeterminate Potential on Advanced Heart Failure
Santiago Alonso Tobar Leitão
, Fernando Luis Scolari
, Jefferson Luís Vieira
, Peter Libby
Introduction
The many processes that contribute to age-related diseases include Harman’s free-radical telomere shortening, inflammaging, and Medewar’s mutation accumulation theory, especially in hematological malignancies., As we age, hematopoietic stem cells may acquire mutations that modulate their function, proliferation, or survival, thus expanding the pool of mutated cells in blood, a process termed clonal hematopoiesis (CH). With the addition of cooperating mutations, CH cells may progress to myelodysplastic syndrome and acute myeloid leukemia at rates ranging from 0.5 to 1% per year. There are dozens of known CH-driver genes, a subset of the known leukemia driver genes, the most frequent of which are DMNT3A, TET2, ASXL1, and JAK2, which account for approximately 80% of all CH mutations. CH increases with age: more than 2% of cells (Variant Allele Fraction [VAF]) will have these mutations in approximately 10% of individuals aged 70 years. Indeed, new and highly sensitive targeted sequencing techniques have shown nearly ubiquitous CH mutations in adults over 30 years of age.
Although the risk of developing a hematologic malignancy is more than 10-fold in individuals with CH, most will have no overt manifestation, hence the term: Clonal Hematopoiesis of Indeterminate Potential (CHIP). Surprisingly, people with CHIP who carry leukocyte clones with mutated leukemia driver genes have a higher risk of developing and/or progressing to non-hematologic conditions of other age-related diseases, such as dementia, osteoporosis, stroke, and cardiovascular diseases. Various mechanisms linked with these diseases are associated with CHIP, including an excessive inflammatory response due to inflammasome activation and enhanced expression of inflammatory cytokines such as IL-1β and IL-6, increased thrombotic potential, and impaired DNA repair.–
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