Early childhood myeloid leukemia is more common in people with Down syndrome, and it’s linked to the acquisition of GATA1 mutations, which produce a short GATA1 isoform termed GATA1s. Congenital anemia is caused by GATA1s-producing mutations in men. For a study, researchers sought to describe two separate families in which multiple individuals acquired acute megakaryoblastic leukemia in childhood due to germline GATA1s-generating mutations. Trisomy 21 or tetrasomy 21 had been acquired in all evaluable leukemias. Characteristics of myeloid leukemia linked with Down syndrome corresponded with those of myeloid leukemia in children under the age of four, including a distinct immunophenotype, a complicated karyotype, gene expression patterns, and treatment sensitivity. 

The findings showed that unique myeloid leukemia is caused by the combination of trisomy 21 and GATA1s-generating mutations, regardless of whether the GATA1 mutation or trisomy 21 is the primary or secondary event, and they suggest that GATA1s and trisomy 21 have unique functional cooperation in leukemogenesis. Germline GATA1s-generating mutations should be included among those linked to a familial propensity to myelodysplastic syndrome and leukemia, according to the family histories.