The striking overlap of early and/or founder events identified in MDS and other myeloid neoplasia [50] is suggestive of a common CHIP/CHOP-like phase in MDS followed by more confined diversification through the acquisition of late and/or transforming aberrancies [33,51], indicating that CH-related genetic lesions are ancestral events to MDS (Figure 2). The gene discussed is C4B; the disease is myelodysplastic syndrome.