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Eltrombopag promotes DNA repair in human hematopoietic stem and progenitor cells

  1. Author:
    Guenther, Kacey L.
    Cheruku, Patali S.
    Cash, Ayla
    Smith, Richard H.
    Alvarado, Luigi J.
    Burkett,Sandra
    Townsley, Danielle M.
    Winkler, Thomas
    Larochelle, Andre

  2. Author Address

    NHLBI, NIH, 9000 Rockville, Bethesda, MD 20892 USA.NCI, NIH, Frederick, MD 21701 USA.
    1. Year: 2019
    2. Date: May
    3. Epub Date: 2019 04 12
  2. Journal: Experimental hematology
  3. ELSEVIER SCIENCE INC,
    1. 73
    2. Pages: 1-6
  5. Type of Article: Article
  6. ISSN: 0301-472X
  1. Abstract:

    A causal link between hematopoietic stem/progenitor cell (HSPC) dysfunction and DNA damage accrual has been proposed. Clinically relevant strategies to maintain genome integrity in these cells are needed. Here we report that eltrombopag, a small molecule agonist of the thrombopoietin (TPO) receptor used in the clinic, promotes DNA double-strand break (DSB) repair in human HSPCs. We found that eltrombopag specifically activates the classic nonhomologous end-joining (C-NHEJ) DNA repair mechanism, a pathway known to support genome integrity. Eltrombopag-mediated DNA repair results in enhanced genome stability, survival, and function of primary human HSPCs, as demonstrated in karyotyping analyses, colony-forming unit assays and after transplantation in immunodeficient NSG mice. Eltrombopag may offer a new therapeutic modality to protect human HSPCs against genome insults. Published by Elsevier Inc. on behalf of ISEH - Society for Hematology and Stem Cells.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.exphem.2019.03.002
  3. PMID: 30986494
  4. View record in Web of Science®
  5. WOS: 000469522500001

Library Notes

  1. Fiscal Year: FY2018-2019
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