All articles tagged with #clonal hematopoiesis
Stanford researchers show that immune cells from the blood can migrate into the aging brain and become microglia, challenging the view of brain immunity as isolated and opening potential new immunotherapy avenues for neurodegenerative diseases like Alzheimer's.
A new study uses accumulated somatic mutations to trace human microglial origins, revealing that marrow-derived cells infiltrate aging brains, resemble microglia, and can become a large fraction of the microglial pool; cohort data also show a protective association between clonal hematopoiesis and Alzheimer's disease, suggesting aging brains recruit marrow-derived myeloid cells into the microglial population.
Analysis of ~736,000 UK Biobank and All of Us genomes shows that age-related mtDNA mutations in blood mainly arise from replication-errors that create low-level, cryptic heteroplasmy, which becomes detectable as people age due to clonal hematopoiesis (CH) expanding certain blood cell clones. The mutations are heavy-strand biased (C>T and A>G), occur at low heteroplasmy, and appear neutral with little evidence of positive selection. GWAS highlight CH-linked loci near TERT, TCL1A and SMC4, and rare-variant analyses implicate CH driver genes; Mendelian randomization indicates CH increases mtSNV burden, not vice versa. CH carriers have more age-accumulating mtSNVs and higher risk of hematologic cancers, suggesting mtSNV burden is a marker of somatic mosaicism. The study proposes a two-step model: random replication errors generate cryptic mtDNA variation, which becomes detectable when CH-driven clonal expansion reveals these variants with age.
Clonal hematopoiesis (CH), the expansion of a few clones of hematopoietic stem cells, is associated with reduced life expectancy and increased risk of hematological neoplasia. A study using whole-genome sequencing of blood samples from over 176,000 participants identified 16,306 cases of CH, with a prevalence of 9.3%. CH was more common in older individuals and strongly associated with smoking. CH was also linked to increased risks of myeloid and lymphoid neoplasia, chronic obstructive pulmonary disease, lung cancer, peripheral artery disease, emphysema, and alcohol abuse. However, no significant association was found between CH and cardiovascular disease or inflammatory conditions. Genetic analysis revealed mutations in known myeloid disease genes, as well as novel associations with other genes. The study provides insights into the epidemiology and genetics of CH and its association with various diseases.
Clonal hematopoiesis, a genetic condition that increases the risk of blood cancer, may also increase the risk of chronic liver disease by promoting inflammation in the liver. Researchers found that mice with clonal hematopoiesis developed more severe liver fibrosis and inflammation when fed a high-fat diet. The study suggests that clonal hematopoiesis may be a previously unrecognized risk factor for chronic liver disease.