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ANIMAL MODELS

Clonal hematopoiesis of indeterminate potential in the companion dog

Leukemia volume 36, pages 1401–1403 (2022)Cite this article

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Clonal Hematopoiesis of Indeterminate Potential (CHIP) is a recently discovered condition of humans characterized by the expansion of a subpopulation of hematopoietic cells in the blood arising from a single hematopoietic stem cell bearing a cancer-associated gene mutation [1,2,3,4]. The frequency of this phenomenon increases with age, and its impact on health is multifold. First, it is a pre-malignant state, with a low, but significant risk of progressing to certain blood cancers [3, 4]. Second, it predisposes individuals to non-neoplastic conditions, such as cardiovascular events, by enhancing macrophage activation and inflammation [5]. For these reasons there is a 30–40% increased risk of all-cause mortality in CHIP patients [1,2,3,4].

In spite of these associations, knowledge of factors, other than aging, that predispose to CHIP and its progression is largely incomplete. There is also an unmet need to develop practical assays for the early detection of CHIP and explore methods of medical intervention that may abrogate progression to more serious disease. To implement these investigations, an appropriate animal model that closely replicates the physiologic consequences of CHIP, including its progression to blood cancer, is essential.

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Fig. 1: Schematic Canis familiaris genes with predicted deleterious CHIP-associated mutations.

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Acknowledgements

We thank the dog owners who allowed donation and banking of their pets DNA and Holly Borghese at The Ohio State Veterinary Biospecimen Repository for the dog DNA samples. This study was funded in part by The Ohio State University Veterinary Biospecimen Repository CTSA Grant (ULTR001070) and P30 CA016058.

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Authors and Affiliations

  1. Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA

    Kimberley Sebastian, Cory Howard & Bonnie K. Harrington

  2. Eli Lilly and Company, Columbus, OH, USA

    H. Gülçin Özer

  3. College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA

    Laura Chadsey

  4. Division of Hematology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, OH, USA

    Arletta Lozanski, Tzyy-Jye Doong & Shelley Orwick

  5. Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Gerard Lozanski

  6. Center for Statistical Analysis and Training, Michigan State University, East Lansing, MI, USA

    Wenjuan Ma

  7. Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH, USA

    William C. Kisseberth

  8. Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    John C. Byrd

Authors
  1. Kimberley Sebastian
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  2. H. Gülçin Özer
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  12. Bonnie K. Harrington
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Contributions

KS collected, analyzed data, and wrote the paper, HGO, CH, LC, AL, TJD and GL collected and analyzed data, WM gave statistical guidance, WCK, JCB and BKH designed the research, analyzed the data, and wrote the paper.

Corresponding author

Correspondence to Bonnie K. Harrington.

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The authors declare no competing interests.

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Sebastian, K., Özer, H.G., Howard, C. et al. Clonal hematopoiesis of indeterminate potential in the companion dog. Leukemia 36, 1401–1403 (2022). https://doi.org/10.1038/s41375-022-01520-5

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