Clonal Hematopoiesis Before, During, and After Human Spaceflight

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. [Display omitted] •Blood samples from twin astronauts were studied for clonal hematopoiesis (CH)•Distinct CH mutations and RNA variant trajectories were found across 4 years•CH was found almost two decades prior to the mean age at which it is typically detected•Longitudinal monitoring of CH is an important disease risk metric for astronauts. Trinchant et al. examined twin astronauts for clonal hematopoiesis (CH). Some high-risk CH clones (TET2 and DNMT3A) were observed two decades before expected, with TET2 decreasing in spaceflight and elevating later post flight. Thus, CH is an important metric for overall cancer and cardiovascular risk in astronauts.