| Literature DB >> 30986494 |
Kacey L Guenther1, Patali S Cheruku1, Ayla Cash1, Richard H Smith1, Luigi J Alvarado1, Sandra Burkett2, Danielle M Townsley1, Thomas Winkler1, Andre Larochelle3.
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.Entities:
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Year: 2019 PMID： 30986494 PMCID： PMC6526067 DOI： 10.1016/j.exphem.2019.03.002
Source DB: PubMed Journal: Exp Hematol ISSN： 0301-472X Impact factor: 3.084