Clonal Hematopoiesis Confers Predisposition to Both Cardiovascular Disease and Cancer: A Newly Recognized Link Between Two Major Killers

Ideas and Opinions17 July 2018Clonal Hematopoiesis Confers Predisposition to Both Cardiovascular Disease and Cancer: A Newly Recognized Link Between Two Major KillersBenjamin L. Ebert, MD, PhD and Peter Libby, MDBenjamin L. Ebert, MD, PhDDana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (B.L.E.)Search for more papers by this author and Peter Libby, MDBrigham and Women's Hospital, Boston, Massachusetts (P.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-0737 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Two scourges of humanity seem to have heretofore unsuspected common roots: cancer and cardiovascular disease. These seemingly disparate disorders share strong associations with aging. As we age, our cells can accumulate somatic genetic mutations, some of which are established drivers of cancer. When a hematopoietic stem cell in the bone marrow acquires certain mutations, it can gain a competitive advantage that gives rise to an expanded clone of leukocytes that circulate in peripheral blood (Figure) (1, 2). Such events are a first step down the path to hematologic cancer, such as myelodysplastic syndrome or acute leukemia. Progression to cancer generally ...References1. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014;371:2488-98. [PMID: 25426837] doi:10.1056/NEJMoa1408617 CrossrefMedlineGoogle Scholar2. Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126:9-16. [PMID: 25931582] doi:10.1182/blood-2015-03-631747 CrossrefMedlineGoogle Scholar3. Wolach O, Sellar RS, Martinod K, Cherpokova D, McConkey M, Chappell RJ, et al. Increased neutrophil extracellular trap formation promotes thrombosis in myeloproliferative neoplasms. Sci Transl Med. 2018;10. [PMID: 29643232] doi:10.1126/scitranslmed.aan8292 CrossrefMedlineGoogle Scholar4. Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A, et al. Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med. 2018;378:1189-99. [PMID: 29601269] doi:10.1056/NEJMoa1716863 CrossrefMedlineGoogle Scholar5. Steensma DP, Ebert BL. Clonal hematopoiesis after induction chemotherapy for acute myeloid leukemia [Editorial]. N Engl J Med. 2018;378:1244-5. [PMID: 29590545] doi:10.1056/NEJMe1802610 CrossrefMedlineGoogle Scholar6. Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377:111-21. [PMID: 28636844] doi:10.1056/NEJMoa1701719 CrossrefMedlineGoogle Scholar7. Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017;355:842-7. [PMID: 28104796] doi:10.1126/science.aag1381 CrossrefMedlineGoogle Scholar8. Libby P, Lichtman AH, Hansson GK. Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity. 2013;38:1092-104. [PMID: 23809160] doi:10.1016/j.immuni.2013.06.009 CrossrefMedlineGoogle Scholar9. Libby P, Nahrendorf M, Swirski FK. Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded “cardiovascular continuum”. J Am Coll Cardiol. 2016;67:1091-103. [PMID: 26940931] doi:10.1016/j.jacc.2015.12.048 CrossrefMedlineGoogle Scholar10. Sano S, Oshima K, Wang Y, MacLauchlan S, Katanasaka Y, Sano M, et al. Tet2-mediated clonal hematopoiesis accelerates heart failure through a mechanism involving the IL-1ß/NLRP3 inflammasome. J Am Coll Cardiol. 2018;71:875-86. [PMID: 29471939] doi:10.1016/j.jacc.2017.12.037 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (B.L.E.)Brigham and Women's Hospital, Boston, Massachusetts (P.L.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0737.Corresponding Author: Peter Libby, MD, Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB-741-G, Boston, MA 02115; e-mail, [email protected]harvard.edu.Current Author Addresses: Dr. Ebert: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215.Dr. Libby: Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, NRB-741-G, Boston, MA 02115.Author Contributions: Conception and design: B.L. Ebert, P. Libby.Analysis and interpretation of the data: B.L. Ebert, P. Libby.Drafting of the article: B.L. Ebert, P. Libby.Final approval of the article: B.L. Ebert, P. Libby.Administrative, technical, or logistic support: P. Libby.Collection and assembly of data: B.L. Ebert, P. Libby.This article was published at Annals.org on 29 May 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoClonal Hematopoiesis Confers Predisposition to Both Cardiovascular Disease and Cancer Abraham Aviv Metrics Cited bySomatic Mutations and Clonal Hematopoiesis as Drivers of Age-Related Cardiovascular RiskImmune and Inflammatory Networks in Myocardial Infarction: Current Research and Its Potential Implications for the ClinicIncreasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and AgingPersonal history of autoimmune disease and other medical conditions and risk of myelodysplastic syndromesCan SARS-CoV-2 induce hematologic malignancies in predisposed individuals? 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A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association ( HFA ) of the European Society of Cardiology ( ESC )TET family dioxygenases and the TET activator vitamin C in immune responses and cancerThe Clinical Challenge of Clonal Hematopoiesis, a Newly Recognized Cardiovascular Risk FactorVascular toxic effects of cancer therapiesRepurposing of drugs approved for cardiovascular diseases: Opportunity or mirage?Association between Clonal Hematopoiesis and Late Nonrelapse Mortality after Autologous Hematopoietic Cell TransplantationTelomeres as Therapeutic Targets in Heart DiseaseInflammation, infection and atherosclerosisGranulopoiesis and Neutrophil Homeostasis: A Metabolic, Daily Balancing ActClonal hematopoiesis: Genes and underlying mechanisms in cardiovascular disease developmentCommon risk factors for heart failure and cancerClonal Hematopoiesis Confers Predisposition to Both Cardiovascular Disease and CancerAbraham Aviv, MDInflammation in atherosclerotic cardiovascular disease 17 July 2018Volume 169, Issue 2Page: 116-117KeywordsBlood cellsCardiovascular disease riskCardiovascular diseasesCellsHematologic malignanciesHematopoiesisLow density lipoproteinMedical risk factorsMutationSomatic mutation ePublished: 29 May 2018 Issue Published: 17 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. 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