Clonal hematopoiesis

Clonal hematopoiesis is the expansion of blood-cell populations descended from a mutated hematopoietic stem cell, often without overt blood cancer. It becomes more common with age and can affect health beyond the blood.

Hematopoietic stem cell: A self-renewing bone marrow cell that produces the many lineages of blood cells. Clonal hematopoiesis begins when one of these cells acquires a mutation and expands.
Hematopoiesis: The production of blood cells from hematopoietic stem and progenitor cells. Clonal hematopoiesis is a change in the ancestry and relative abundance of hematopoietic cells.
Myeloid neoplasm: A clonal blood cancer arising from myeloid-lineage cells, including myelodysplastic syndromes and acute myeloid leukemia. Clonal hematopoiesis is clinically monitored partly because some clones precede these cancers.
DNMT3A: A gene encoding a DNA methyltransferase involved in epigenetic regulation and blood-cell development. Mutations in DNMT3A are among the most frequent drivers of age-related clonal hematopoiesis.
Somatic mutation: A DNA change acquired by a cell after conception and passed to its descendants. A mutation in a blood-forming stem cell can mark the descendants of its clone.
Clonal hematopoiesis of indeterminate potential: Clonal hematopoiesis with a qualifying somatic mutation and no unexplained cytopenia or blood cancer. This diagnostic category captures many clonal cases found in people without a blood disorder.
Cardiovascular disease: A group of disorders affecting the heart and blood vessels. Clonal hematopoiesis is associated with elevated cardiovascular risk, especially for certain mutations.
TET2: A gene encoding an enzyme that modifies DNA methylation marks and influences cell differentiation. TET2-mutant clones are common and have been linked to inflammatory and cardiovascular effects.
Clonal selection: The process by which cells with heritable advantages become more abundant than competing cells. Age-related pressures can favor mutant blood-cell clones over other stem-cell lineages.
Clonal cytopenia of undetermined significance: Persistent unexplained low blood counts accompanied by one or more somatic mutations in blood cells. Cytopenias distinguish this related condition from clonal hematopoiesis without unexplained low counts.

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