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ISAL 2017 | Recognizing clonal hematopoiesis – diagnostic challenges and clinical relevance

Rafael Bejar, MD, PhD, from UC San Diego, San Diego, CA, discusses the implications of recognizing clonal hematopoiesis at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. He explains the concept of clonal hematopoiesis, where cells in the bone marrow, particularly stem cells, acquire mutations which give them a selective advantage, resulting in these cells growing and dominating the marrow. This is recognized to be a precursor event for a number of diseases, including myeloid disorders and other types of blood cancer, however it is still being studied how the presence of these abnormally expanded cells infers a risk for subsequent disease development. Dr Bejar describes his talk at ISAL 2017 on recognizing clonal hematopoiesis, and assessing its meaning, as well as adverse and favorable aspects of expanded clones. Clonal hematopoiesis is remarkably common, particularly in older people, where it is found in 10 – 15% of the population, and can make up between 10 – 20% of the blood cells in the marrow and peripheral blood. A slightly increased risk of developing blood cancer is observed in these individuals; however, it is not well understood what leads to progression from clonal hematopoiesis to blood cancer. Dr Bejar introduces other contexts in which clonal hematopoiesis is seen, for example in patients with aplastic anemia, characterized by an immune response against blood cells, where small mutant clones are seen in almost all patients, particularly those who are older. While some mutations are an attempt at immunological escape, other mutations are more similar to mutations seen in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), indicating that these clones have increased their survival by increases proliferation or resistance to apoptosis, and it is patients with these clones who are at risk of subsequently developing a problem or dying of aplastic anemia. Dr Bejar goes on to point out that the incidence of clonal hematopoiesis may be increased in individuals with low baseline blood counts. Genetic sequencing of patients who are suspected of having a blood disorder but do not meet clinical diagnostic criteria has revealed that around 40% of these patients have clonal hematopoiesis. This can help to identify which patients are at greatest risk of developing a blood disorder, and should be followed up, and those who may have an alternative cause of their low blood counts but can be reassured that they are unlikely to develop a problem. Dr Bejar indicates that this can change clinical practice by predicting patient outcomes, however he hopes that in future, interventions will be available at this stage, so that progression from clonal hematopoiesis can be prevented in those patients who are at risk.

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