IBC 2025 | Understanding age-related clonal hematopoiesis versus context-relevant clonal hematopoiesis

Yeah, so you know as the last decade has progressed, we’ve understood that clonal hematopoiesis is clearly segregated into two subtypes. The first being age-related clonal hematopoiesis. These are large population-based studies that have been done. These are seen in aging individuals. They have a low risk of progression to hematological malignancies, have associations with cardiovascular disease and other comorbidities. But in academic medical centers, what we more frequently encounter is what I refer to as context-relevant clonal hematopoiesis. So these are clonal hematopoiesis or CHIP mutations that arise in the hematopoietic stem and progenitor cells in response to things that are happening in the individual’s body, such as other tumors, more importantly therapies for the tumors. These are genotoxic agents. They’re radiation-based therapies or radioligands. They can also be seen in individuals who have hereditary problems causing bone marrow failure or increase their risk for leukemia. So they develop a very unique spectrum of CHIP mutations. These mutations are highly relevant because unlike the age-related clonal hematopoiesis, these tend to progress much quicker, causing hematopoietic dysfunction and a very dangerous outcome which is therapy-related myeloid neoplasms. So these are conditions such as acute myeloid leukemia where treatment responses are quite poor and the morbidity and mortality are very high.

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