Different from myeloid malignancies, mutations in CH generally occur in a small percentage of blood cells as reflected by the variant allele frequency (VAF), which is the number of variant reads relative to the total number of reads at a given mutation position.1,2 Individuals with CH have a higher risk of developing haematological malignancies, including acute myeloid leukaemia.3,5,6 Based on these findings, CH is increasingly recognized as a precursor condition for myeloid malignancies, representing an early stage in the stepwise process of clonal selection, with subsequent mutations that may result in full-blown leukaemia.7 The acronym “Clonal Hematopoiesis of Indeterminate Potential” (CHIP) was first proposed to describe the presence of CH in otherwise healthy individuals, at a VAF ≥2%.8 CH occurs at higher frequencies when mutation screening by Next Generation Sequencing (NGS) is ordered for patients presenting with cytopenias that remain unexplained after careful evaluation and nondiagnostic bone marrow.9 “Clonal Cytopenia of Undetermined Significance” (CCUS) is coined to describe the presence of CH clones in such individuals with unexplained cytopenia, that do not meet established criteria for myeloid malignancy. Gene-specific fitness effects determining clonal outgrowth were shown in the Lothian Birth Cohort.16 Fabre et al. further tracked gene-specific clonal dynamics in peripheral blood samples from 385 adults in the Sardinia longitudinal study.17 We recently reported growth rates for common myeloid driver gene mutations based on sequential VAF measurements in 3359 individuals ≥60 years from the population-based Lifelines cohort.18 These studies show that DNMT3A and TP53-mutated clones are characterized by very limited clonal expansion, whereas highest growth rates are observed for clones with mutations in the splicing factor genes (SF3B1, SRSF2 and U2AF1) and JAK2. Other markers of prognostic relevance include mean corpuscular volume (MCV) and red blood cell distribution width (RDW).6,20 Finally, the joint role of gene mutations and clonal chromosomal abnormalities in haematological malignancy development warrants further study.24 ‘GENOTYPE (G) + ENVIRONMENT (E) = PHENOTYPE (P)’ Apart from gene-specific trajectories, there is still considerable inter-individual variation in growth trajectories, even when such individuals carry the exact same mutation.