Age related clonal hematopoiesis

Inevitably, aging is accompanied by increasing random mutations in hematopoietic stem cells (HSCs). “When a mutation gives the stem cell proliferative advantage, and you find the same mutation in many cells, this is called clonal hematopoiesis. The incidence of clonal hematopoiesis increases with age”, said Dr Michael Heuser (Hannover Medical School, Germany) in a Basic Science-in-Focus session.

Clonal hematopoiesis is quite common, and is found in 13% of the general population aged 70-80 years. Genes that are most often mutated in clonal hematopoiesis include DNMT3A, TET2 and ASXL1. Age-related clonal hematopoiesis is associated with an increased risk of hematologic malignancies (11-13 fold) and therapy-related malignancies. Moreover, these individuals have a higher risk of coronary heart disease and stroke, especially those with a large clone size. One explanation was the observation that TET2-deficient stem cells may mature to TET2-deficient macrophages, which produce IL-1b and create an inflammatory environment that promotes the formation of atherosclerotic plaques.

Clonal hematopoiesis is detected in 64% of patients with unexplained cytopenias, and these patients have a much higher risk of developing myeloid neoplasia than cytopenic patients without a mutation. Clonal hematopoiesis also may affect the outcome in younger aplastic anemia patients, depending on the mutation, and may obscure MRD detection in AML patients.

Heuser proposed an algorithm to analyze patients with unexplained cytopenia for clonal hematopoiesis, and if necessary treat them for cardiovascular risk factors, and monitor them for hematologic neoplasia and therapy-related malignancies.  

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