TitleClonal Hematopoiesis Before, During, and After Human Spaceflight.
Publication TypeJournal Article
Year of Publication2020
AuthorsMencia-Trinchant, Nuria, MacKay Matthew J., Chin Christopher, Afshinnekoo Ebrahim, Foox Jonathan, Meydan Cem, Butler Daniel, Mozsary Christopher, Vernice Nicholas A., Darby Charlotte, Schatz Michael C., Bailey Susan M., Melnick Ari M., Guzman Monica L., Bolton Kelly, Braunstein Lior Z., Garrett-Bakelman Francine, Levine Ross L., Hassane Duane C., and Mason Christopher E.
JournalCell Rep
Volume33
Issue10
Pagination108458
Date Published2020 12 08
ISSN2211-1247
KeywordsAdult, Astronauts, Clonal Hematopoiesis, Clone Cells, Dioxygenases, DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, DNA-Binding Proteins, Female, Hematologic Neoplasms, Hematopoiesis, Humans, Male, Middle Aged, Mutation, Neoplasms, Risk Factors, Space Flight, Time Factors, Weightlessness
Abstract

<p>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.</p>

DOI10.1016/j.celrep.2020.108458
Alternate JournalCell Rep
PubMed ID33242405
PubMed Central IDPMC9398182
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
R01 AI151059 / AI / NIAID NIH HHS / United States
R01 CA249054 / CA / NCI NIH HHS / United States
R21 CA176362 / CA / NCI NIH HHS / United States