Loss of HPTM marks such as those observed in our analysis of JMML HSPCs are signature events in numerous malignancies, including H3K23ac in solid tumor models such as breast cancer, KRAS-mutated colorectal cancer, and non-small-cell lung cancer [51,57]; H3S10ph in aggressive solid tumors, including colon cancer [58,59]; and H3K36me2, H3K36me2, and H3K27me2 in leukemic transformation in AML [60] and poor AML patient prognosis [61,62]. This evidence concerns the gene KRAS and acute myeloid leukemia.