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| http://dx.doi.org/10.1016/j.stem.2025.07.011 | DOI Listing |
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is the second most frequently mutated gene in clonal hematopoiesis of indeterminate potential (CHIP), driving hematopoietic stem cell clonal expansion and increasing the risk of myeloid malignancies. Affected individuals often develop atherosclerotic cardiovascular disease, exacerbated by hyperinflammatory -mutant macrophages. Here, we show that the XPO1 nuclear export inhibitor eltanexor significantly reduces atherosclerotic plaque formation in a mouse model of -mutant CHIP.
View Article and Find Full Text PDFTET2-mutant myeloid cells mitigate Alzheimer's disease progression via CNS infiltration and enhanced phagocytosis in mice.
Cell Stem Cell
August 2025
Division of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer's disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and β-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow.
View Article and Find Full Text PDFCell-extrinsic factors contribute toward myeloid-biased expansion in Tet2-mutant clonal hematopoiesis.
Exp Hematol
August 2025
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO. Electronic address:
Hematopoietic stem cells (HSCs) accumulate mutations with age, and some mutations give cells a competitive edge, leading to clonal hematopoiesis (CH)-a condition linked to blood cancers and other diseases like diabetes and cardiovascular disease. TET2, a gene highly expressed in HSCs, is frequently mutated in CH and several myeloid malignancies. TET2 mutations cause increased stem cell numbers and a shift toward myeloid differentiation, promoting malignancy.
View Article and Find Full Text PDFTumor-Infiltrating Clonal Hematopoiesis.
N Engl J Med
April 2025
Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London.
Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients with cancer. CHIP mutations with high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis (TI-CH). The frequency of TI-CH and its effect on tumor evolution are unclear.
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