In contrast, the co-mutational pattern for RAD21, SMC3, and SMC1A was distinct from STAG2, and confirmed enrichment for de novo and pan AML ontogeny-defining mutations NPM1 and FLT3 (OR = 4.4 and 2.3; FDR = 1×10–5 and 0.01, respectively). Here, STAG2 is linked to acute myeloid leukemia.