Clonal Hematopoiesis Before, During, and After Human Spaceflight

Nuria Mencia Trinchant, Matthew J. MacKay, Christopher Chin, Ebrahim Afshinnekoo, Jonathan Foox, Cem Meydan, Daniel Butler, Christopher Mozsary, Nicholas A. Vernice, Charlotte Darby, Michael C. Schatz, Susan M. Bailey, Ari M. Melnick, Monica Guzman, Kelly Bolton, Lior Z. Braunstein, Francine Garrett-Bakelman, Ross L. Levine, Duane Hassane, Christopher E. Mason

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Clonal hematopoiesis (CH) occurs when blood cells harboring an advantageous mutation propagate faster than others. These mutations confer a risk for hematological cancers and cardiovascular disease. Here, we analyze CH in blood samples from a pair of twin astronauts over 4 years in bulk and fractionated cell populations using a targeted CH panel, linked-read whole-genome sequencing, and deep RNA sequencing. We show CH with distinct mutational profiles and increasing allelic fraction that includes a high-risk, TET2 clone in one subject and two DNMT3A mutations on distinct alleles in the other twin. These astronauts exhibit CH almost two decades prior to the mean age at which it is typically detected and show larger shifts in clone size than age-matched controls or radiotherapy patients, based on a longitudinal cohort of 157 cancer patients. As such, longitudinal monitoring of CH may serve as an important metric for overall cancer and cardiovascular risk in astronauts.

Original languageEnglish
Article number108458
JournalCell Reports
Volume33
Issue number10
DOIs
StatePublished - Dec 8 2020

Keywords

  • CHIP
  • DNMT3A
  • NASA
  • TET2
  • astronaut
  • clonal hematopoiesis
  • radiation
  • variant allele frequency

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