We demonstrated that STAG2 mutations are associated with secondary AML ontogeny, are usually acquired at MDS or MDS/MPN stage, and co-occur with other secondary ontogeny-defining mutations, such as ASXL1, SRSF2, and RUNX1. Our data are in agreement with initial reports identifying STAG2 as one of the eight secondary AML ontogeny defining lesions [21], as well as the 2022 International Consensus Classification which uses STAG2 as an AML-MR defining mutation for classification of AML [40, 41]. Here, STAG2 is linked to myelodysplastic syndrome.