DNMT3A and cyclic hematopoiesis: DNMT3A is by far the most frequently altered gene in CH (Buscarlet et al., 2017; Coombs et al., 2017; Genovese et al., 2014; Jaiswal et al., 2014; van Zeventer et al., 2021; Xie et al., 2014; Young et al., 2016) with the majority of mutations consistent with a heterozygous loss of function (∼50%, truncating indels, splice, and nonsense; Brunetti et al., 2017; Venugopal et al., 2021).