GATA1 germline mutations predispose to leukemia

Early childhood myeloid leukemia is more common in people with Down syndrome and is linked to the acquisition of GATA1 mutations, which produce a short GATA1 isoform called GATA1. Congenital anemia is caused by GATA1-producing mutations in males. For one study, researchers sought to describe two distinct families in which several people contracted acute megakaryoblastic leukemia in childhood due to germline GATA1-generating mutations. Trisomy 21 or tetrasomy 21 had been acquired in all evaluable leukaemias. Features of Down syndrome-related myeloid leukemia were consistent with those of myeloid leukemia in children under four years of age, including distinct immunophenotype, complicated karyotype, gene expression profiles, and treatment sensitivity.

The results showed that single myeloid leukemia is caused by the combination of trisomy 21 and GATA1 generative mutations, whether the GATA1 mutation or trisomy 21 is the primary or secondary event, and they suggest that GATA1 and trisomy 21 have unique functional cooperation in leukemogenesis. Germline mutations that generate GATA1s should be included among those linked to a familial propensity for myelodysplastic syndrome and leukemia, based on family history.

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