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Ideas and Opinions |17 July 2018

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

Benjamin L. Ebert, MD, PhD; Peter Libby, MD

Article, Author, and Disclosure Information
Author, Article, and Disclosure Information
This article was published at Annals.org on 29 May 2018.
  • 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, plibby@bwh.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.

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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 requires acquisition of additional somatic mutations in the cells in the expanded clone of leukocytes, as depicted in the Figure.
This premalignant state for hematologic cancer, termed “clonal hematopoiesis of indeterminate potential” (CHIP), is analogous to monoclonal gammopathy of unknown significance, a premalignant state for multiple myeloma. The presence of a somatic mutation associated with hematologic cancer in the peripheral blood at a variant allele frequency of at least 2% in the absence of hematologic cancer defines CHIP.
CHIP is common. Septuagenarians have a greater than 10% chance of having such a clone, and prevalence continues to increase markedly with age (1). Persons with CHIP have a more than 10-fold increased risk for hematologic cancer, although most never develop myelodysplastic syndrome or leukemia (1, 2). After induction chemotherapy for acute myeloid leukemia, those with residual populations of peripheral blood...
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Ebert BL, Libby P. Clonal Hematopoiesis Confers Predisposition to Both Cardiovascular Disease and Cancer: A Newly Recognized Link Between Two Major Killers. Ann Intern Med. [Epub ahead of print 29 May 2018]169:116–117. doi: 10.7326/M18-0737

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Published: Ann Intern Med. 2018;169(2):116-117.

DOI: 10.7326/M18-0737

Published at www.annals.org on 29 May 2018

©
2018 American College of Physicians
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