The accumulation of acquired somatic mutations is a natural consequence of ageing, but the pathophysiological implications of these mutations beyond cancer are only beginning to be understood. Most somatic mutations are functionally neutral, but a few may confer a competitive advantage to a stem cell, driving its clonal expansion. When such a mutation arises in haematopoietic stem cells, it leads to clonal haematopoiesis, in which a significant proportion of blood cells originate from the mutant stem cell and share the same mutation. Clonal haematopoiesis of indeterminate potential (CHIP), a specific subset of clonal haematopoiesis driven by myeloid leukaemia-related somatic mutations, has been linked to a higher risk of various age-related conditions, particularly CVD, by exacerbating inflammatory responses. Emerging evidence suggests that CHIP may also contribute to the pathogenesis of type 2 diabetes and some of its complications. This review synthesises current knowledge on CHIP and its potential as a novel risk factor for type 2 diabetes, highlighting the need for further research to clarify this relationship and to explore its potential value in developing personalised preventive care strategies for type 2 diabetes and related conditions.
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http://dx.doi.org/10.1007/s00125-025-06393-8 | DOI Listing |
Nat Commun
March 2025
Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, M5G 1L7, Canada.
Ten-Eleven Translocation-2 (TET2) mutations drive the expansion of mutant hematopoietic stem cells (HSCs) in clonal hematopoiesis (CH). However, the precise mechanisms by which TET2 mutations confer a competitive advantage to HSCs remain unclear. Here, through an epigenetic drug screen, we discover that inhibition of disruptor of telomeric silencing 1-like (DOT1L), a H3K79 methyltransferase, selectively reduces the fitness of Tet2 knockout (Tet2) hematopoietic stem and progenitor cells (HSPCs).
View Article and Find Full Text PDFDiabetologia
March 2025
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
The accumulation of acquired somatic mutations is a natural consequence of ageing, but the pathophysiological implications of these mutations beyond cancer are only beginning to be understood. Most somatic mutations are functionally neutral, but a few may confer a competitive advantage to a stem cell, driving its clonal expansion. When such a mutation arises in haematopoietic stem cells, it leads to clonal haematopoiesis, in which a significant proportion of blood cells originate from the mutant stem cell and share the same mutation.
View Article and Find Full Text PDFEur J Heart Fail
March 2025
Second Department of Cardiology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Aims: Clonal haematopoiesis (CH) is recognized as a significant risk factor for various non-haematologic conditions, including cardiovascular diseases. However, recent studies examining its relationship with heart failure (HF) have reported conflicting findings. To address these inconsistencies, the present meta-analysis aimed to evaluate the association of CH with the incidence and clinical outcomes of HF.
View Article and Find Full Text PDFCurr Opin Hematol
March 2025
Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Cheeloo College of Medicine.
Purpose Of Review: This review encompasses the recently published information on clonal hematopoiesis of indeterminate potential (CHIP) and discusses its future prospects. By announcing advances in the research of CHIP risk factors and related diseases, with the purpose of offering new insights to treat both hematologic and nonhematologic disorders.
Recent Findings: The majority of studies have shown that CHIP is a common biological condition associated with aging and the incidence of clonal hematopoiesis increases with age.
J Intern Med
March 2025
Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background: Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related expansion of blood cells carrying preleukemic mutations, is associated with immune aging. This study aimed to investigate the association between CHIP and established autoimmune diseases.
Methods: We analyzed baseline data from 456,692 UK Biobank participants with available whole-exome sequences.
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