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BSH 2023 | Understanding genetic and non-genetic mechanisms involve in AML disease progression

Paresh Vyas, MRCP, FRCP, FRCPath, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK, briefly discusses genetic and non-genetic mechanisms involved in disease progression and transformation in acute myeloid leukemia (AML). Prof. Vyas notes new research exploring the involvement of inflammation and concludes by emphasizing the importance of better identifying patients at high risk of progression to AML and developing early interventions with reduced toxicity. This interview took place at the 63rd Annual Scientific Meeting of the British Society for Haematology (BSH) 2023, held in Birmingham, UK.

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Transcript (edited for clarity)

Over the last decade almost, we’ve understood that myeloid malignancies like acute myeloid leukemia, often begin many, many years prior to the patient presenting with conditions like clonal hematopoiesis. These are conditions where a somatic mutation affords a blood stem cell a survival advantage. This is often the first step on the road to AML. Not all patients will eventually transform to AML, but what we’re beginning to understand is that there are not only the acquisition of additional genetic mutations that allow transformation to occur, but there are non-genetic mechanisms, for example, concurrent inflammation...

Over the last decade almost, we’ve understood that myeloid malignancies like acute myeloid leukemia, often begin many, many years prior to the patient presenting with conditions like clonal hematopoiesis. These are conditions where a somatic mutation affords a blood stem cell a survival advantage. This is often the first step on the road to AML. Not all patients will eventually transform to AML, but what we’re beginning to understand is that there are not only the acquisition of additional genetic mutations that allow transformation to occur, but there are non-genetic mechanisms, for example, concurrent inflammation. This work is still in its infancy, but clearly it’s important because if we could identify patients destined to develop AML and have interventions that are significantly less toxic early on, this would be of benefit to patients.

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