Down syndrome acute megakaryoblastic leukemia (DS-AMKL) is associated with somatic mutations in GATA1. Mutations in exon 2 result in an increase in the short form of GATA1 (GATA1s) protein via alternative splicing of the full-length GATA1 transcript. Here, GATA1 is linked to acute megakaryoblastic leukemia in down syndrome.