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bioRxiv · 10.1101/2025.05.02.651715

Clonal hematopoiesis driven by Dnmt3a mutations promotes metabolic disease development

Yan, B.·Yuan, Q.·Kaur, P.·Mckee, A. R.·Shabashvili, D. E.·Guryanova, O. A.
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Abstract

Clonal hematopoiesis (CH) is associated with an increased risk of non-hematologic chronic diseases including metabolic disorders, yet the causality remains poorly defined. DNMT3A is the most frequently altered gene in CH, commonly through monoallelic loss-of-function (LOF) and Arg882His (RH) hotspot mutations. Here we demonstrate in a mouse model that CH driven by Dnmt3a RH and especially LOF promotes obesity, diabetes, and chronic liver disease, further exacerbated by high-fat diet (HFD).

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Yan, B., Yuan, Q., Kaur, P., Mckee, A. R., Shabashvili, D. E., Guryanova, O. A.. 2025-05-08. Clonal hematopoiesis driven by Dnmt3a mutations promotes metabolic disease development. https://doi.org/10.1101/2025.05.02.651715

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