Multiomic profiling of human clonal hematopoiesis reveals genotype and cell-specific inflammatory pathway activation.

Autor:	Heimlich JB; Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Bhat P; Vanderbilt University School of Medicine, Nashville, TN., Parker AC; Vanderbilt University School of Medicine, Nashville, TN., Jenkins MT; Vanderbilt University School of Medicine, Nashville, TN., Vlasschaert C; Department of Medicine, Queen's University, Kingston, ON, Canada., Ulloa J; Division of Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Van Amburg JC; Division of Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Potts CR; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Olson S; Division of Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Silver AJ; Vanderbilt University School of Medicine, Nashville, TN., Ahmad A; Division of Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Sharber B; Division of Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Brown D; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Hu N; Division of Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., van Galen P; Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA.; Ludwig Center at Harvard, Harvard Medical School, Boston, MA., Savona MR; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.; Vanderbilt-Ingram Cancer Center, Program in Cancer Biology, and Center for Immunobiology, Nashville, TN.; Center for Immunobiology, Vanderbilt University School of Medicine, Nashville, TN., Bick AG; Division of Genomic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN., Ferrell PB; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2024 Jul 23; Vol. 8 (14), pp. 3665-3678.
DOI:	10.1182/bloodadvances.2023011445
Abstrakt:	Abstract: Clonal hematopoiesis (CH) is an age-associated phenomenon that increases the risk of hematologic malignancy and cardiovascular disease. CH is thought to enhance disease risk through inflammation in the peripheral blood.1 Here, we profile peripheral blood gene expression in 66 968 single cells from a cohort of 17 patients with CH and 7 controls. Using a novel mitochondrial DNA barcoding approach, we were able to identify and separately compare mutant Tet methylcytosine dioxygenase 2 (TET2) and DNA methyltransferase 3A (DNMT3A) cells with nonmutant counterparts. We discovered the vast majority of mutated cells were in the myeloid compartment. Additionally, patients harboring DNMT3A and TET2 CH mutations possessed a proinflammatory profile in CD14+ monocytes through previously unrecognized pathways such as galectin and macrophage inhibitory factor. We also found that T cells from patients with CH, although mostly unmutated, had decreased expression of GTPase of the immunity associated protein genes, which are critical to T-cell development, suggesting that CH impairs T-cell function. (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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