The pathophysiology of Fanconi anemia, dyskeratosis congenita and therapy-related MDS suggests that chronic HSC apoptosis can be attributed, at least in part, to chronic DNA damage checkpoint signaling, with ATM/ATR, CHK1, CHK2 and TP53 being central players.109 These checkpoints preserve genetic stability and act as a barrier to malignant transformation,110 thus evolving tumor cells are in need to inactivate them. Here, CHEK2 is linked to myelodysplastic syndrome.