![]() ![]() īeyond increasing the risk of primary or secondary malignancies, clinical outcomes in other disease processes tend to be negatively affected by the presence of CH although there are some identified exceptions. CH has been primarily viewed as a precursor to myeloid malignancies such as acute myeloid leukemia or myelodysplastic syndrome, though it is recognized that some clonal expansions can predispose individuals to lymphoid malignancies as well, leading to the characterization of some mutations and mCAs as either myeloid or lymphoid CH. CH of indeterminate potential (CHIP) is a subset of CH and is generally restricted to somatic mutations in genes associated with hematologic malignancy ( DNMT3A, TET2, ASXL1, JAK2, TP53, etc.) with a minimum variant allele frequency (VAF) of 2%. ![]() When these genetic lesions lead to clonal expansion of a population in the absence of a malignancy or cytopenia, it is referred to as CH. Somatic mutations and mosaic chromosomal alterations (mCAs) accumulate in hematopoietic stem cells (HSCs) and their cellular progeny as individuals age. Blockade of IL-1β or JAK2 signaling are potential avenues for preventing CH-caused cardiovascular morbidity and mortality. SummaryĬH mutations lead to harmful inflammation and arterial wall invasion by bone marrow-derived cells resulting in poor cardiovascular health and outcomes. Mechanistically, some adverse outcomes are caused by macrophage secretion of IL-1β and IL-6, neutrophil invasion of injured myocardium, and T-cell skewing towards inflammatory phenotypes. Recent FindingsĪ combination of clinical outcome studies and mouse models have offered strong evidence that CH mutations either correlate with or cause atherosclerosis, diabetes mellitus, chronic kidney disease, heart failure, pulmonary hypertension, aortic aneurysm, myocardial infarction, stroke, aortic stenosis, poor outcomes following transcatheter aortic valve replacement (TAVR) or orthotopic heart transplant, death or need of renal replacement therapy secondary to cardiogenic shock, death from cardiovascular causes at large, and enhance anthracycline cardiac toxicity. CH has been linked to increased risk of blood cancers, but CH has also been linked to adverse cardiovascular outcomes. Samani, Matthew J.Hematopoiesis (CH) refers to the expansion of hematopoietic stem cell clones and their cellular progeny due to somatic mutations, mosaic chromosomal alterations (mCAs), or copy number variants which naturally accumulate with age. Van Sterkenburg, Jean Paul De Vries, Kari Stefansson, John R. Johnson, Christer Betsholtz, Arno Ruusalepp, Oscar Franzén, Eric E. Ferrell, Per Eriksson, Lasse Folkersen, Anders Franco-Cereceda, John D. Nelson, Natzi Sakalihasan, Audrey Courtois, Robert E. Bradley, Kathleen Stirrups, Jonathan Golledge, Paul E. Teijink, Cisca Wijmenga, Jacqueline De Graaf, Lambertus A. Matthiasson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Jan D. Clough, Gillian Cockerill, Hany Hafez, D. Verissimo, Suzannah Bumpstead, Stephen A. ![]() Merriman, Grzegorz Oszkinis, Silvia Galora, Claudia Saracini, Rosanna Abbate, Raffaele Pulli, Carlo Pratesi, Athanasios Saratzis, Ana R. ![]() Williams, Wenhua Wei, Ross Blair, Andrew A. Elmore, Anurag Verma, Sarah Pendergrass, Iftikhar J. Baas, Betti Giusti, Ewa Strauss, Femke N.G. Jones, Gerard Tromp, Helena Kuivaniemi, Solveig Gretarsdottir, Annette F. ![]()
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