DS-AMKL pathogenesis. In utero truncating mutations in GATA1 lead to a TMD in the neonatal period that resolves in the absence of treatment. Residual cells either undergo apoptosis or acquire additional cooperating mutations leading to overt AMKL with an average latency of 3 years. Recurrently targeted genes include but are not limited to cohesin complex components, CTCF, the PRC2 complex, and kinase-signaling genes. Of the 26 sequenced DS-AMKL cases that carry mutations in cohesin, 6 contained mutations in a PRC2 complex gene as well as a kinase as shown in this example.²⁵  Cohesin mutation, ●; GATA1 mutation, ★; kinase mutation, ▲; PRC2 mutation, ▪; Trisomy 21, ×××.