GATA1 and cooperating mutations in myeloid leukaemia of Down syndrome

IUBMB Life. 2020 Jan;72(1):119-130. doi: 10.1002/iub.2197. Epub 2019 Nov 26.


Myeloid leukaemia of Down syndrome (ML-DS) is an acute megakaryoblastic/erythroid leukaemia uniquely found in children with Down syndrome (constitutive trisomy 21). It has a unique clinical course, being preceded by a pre-leukaemic condition known as transient abnormal myelopoiesis (TAM), and provides an excellent model to study multistep leukaemogenesis. Both TAM and ML-DS blasts carry acquired N-terminal truncating mutations in the erythro-megakaryocytic transcription factor GATA1. These result in exclusive production of a shorter isoform (GATA1s). The majority of TAM cases resolve spontaneously without the need for treatment; however, around 10% acquire additional cooperating mutations and transform to leukaemia, with differentiation block and clinically significant cytopenias. Transformation is driven by the acquisition of additional mutation(s), which cooperate with GATA1s to perturb normal haematopoiesis.

Keywords: Gata1; acute myeloid leukaemia; cohesin; trisomy 21.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Down Syndrome / genetics
  • Down Syndrome / pathology*
  • GATA1 Transcription Factor / genetics*
  • Humans
  • Leukemia, Myeloid / genetics
  • Leukemia, Myeloid / pathology*
  • Mutation*


  • GATA1 Transcription Factor