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ASH 2024 | Mutation-specific differences in the relationship between obesity and clonal hematopoiesis
Benjamin Rolles, MD, Brigham and Women’s Hospital, Boston, MA, comments on research being undertaken at the Mullally Lab to determine the drivers of the progression of clonal hematopoiesis to myeloproliferative neoplasms (MPNs). A study using data from the UK Biobank found a negative association between obesity and the JAK2 mutation, leading to the development of a mouse model to investigate the impact of obesity on clonal dynamics and potentially elucidate lifestyle factors that may impact the development of MPNs. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
What is the Mullally Lab focused for several years on MPN disease? But we got more and more interested in focusing on clonal haematopoiesis. And the main reason for that is that we know for a few years now that the initial mutation in a stem cell, for example the mutation of a JAK2 driver, occurs very early in life and it takes decades till the clone expands and the patient develops MPN and we are very much interested now in finding factors that promote or impair clonal expansion and due to that fact we screened the UK Biobank, a huge database with healthy individuals, and screened them for factors that are associated with mutations of clonal hematopoiesis and lifestyle factors and comorbidities...
What is the Mullally Lab focused for several years on MPN disease? But we got more and more interested in focusing on clonal haematopoiesis. And the main reason for that is that we know for a few years now that the initial mutation in a stem cell, for example the mutation of a JAK2 driver, occurs very early in life and it takes decades till the clone expands and the patient develops MPN and we are very much interested now in finding factors that promote or impair clonal expansion and due to that fact we screened the UK Biobank, a huge database with healthy individuals, and screened them for factors that are associated with mutations of clonal hematopoiesis and lifestyle factors and comorbidities. And we found out that obesity has a negative association with the JAK2 mutation. And we built, based on that finding, we established a new mouse model and tried to find out if that’s a true biological finding. And we think our mouse model showed that JAK2 mutant stem cells behave differently in an obese environment, indicating that there are certain lifestyle factors or comorbidities that can really impact clonal dynamics over time. So that maybe some individuals with clonal hematopoiesis develop MPN disease or leukemia or don’t develop MPN disease or leukemia. And we are right now trying to find out these factors to develop hopefully future treatments.
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