Proposed model for ERG deficiency syndrome–associated phenotypes showing adaptive/maladaptive events in ERG heterozygous carriers. It is proposed that ERG carriers harbor a threshold of activity that is insufficient under certain physiological and environmental stressors, thus leading to a range of phenotypic outcomes (top panel). Malignant cells (yellow cells). Maladaptive and adaptive events observed in our study (arrow). Other potential (maladaptive/adaptive) somatic events seen in other BMF and/or HM predisposition genes^63-65 (dotted arrow) or hypothetical events (question mark preceding dotted arrow). Game of clones (bottom panel). The development of different physiological outcomes in patients is the consequence of a game of clones in which context-dependent competitive fitness of the clone(s) determines progression and the observed outcome. Notably, adaptive and maladaptive events and subsequent clonal selection may occur simultaneously. The clonal output shown is based on mature blood cells, reflecting collectively the impact on mature and stem and progenitor cells.