Compared to CHIP and early-stage MDS, LSCs in sAML and late-stage MDS have acquired mutations that confer uncontrolled growth, such as NRAS, and inhibition of apoptosis, such as TP53. Together with epigenetic abnormalities, these oncogenic mutations cause blast cell numbers to increase and inhibit differentiation, which is characteristic of the MDS-to-sAML transformation [1]. The gene discussed is TP53; the disease is myelodysplastic syndrome.