Progression of myeloid leukemia in children with DS.GATA1 mutations commonly occur in utero as early as week 21 of gestation in hematopoietic progenitors with trisomy 21. The resulting TMD is initially polyclonal, with multiple distinct GATA1-mutant clones. The GATA1 mutational burden diminishes shortly after birth as the TMD resolves. Over the course of one to three years, a persistent GATA1-mutant clone may acquire a tertiary mutation, which leads to clonal expansion and acute megakaryocytic leukemia.