TO THE EDITOR:

Children diagnosed with Down syndrome (DS) have a 150-fold increased risk of developing a unique acute myeloid leukemia (ML-DS) within the first 4 years of life.1,2  ML-DS is preceded by a fetal/neonatal myeloproliferative disorder, transient abnormal myelopoiesis (TAM). ML-DS and TAM require mutations in the X-chromosome encoded erythro-megakaryocyte transcription factor GATA1.3-7  In normal human GATA1-expressing cells, 2 GATA1 isoforms are detected; a full-length 414-amino-acid protein (GATA1fl) and an N-terminal truncated 331-amino-acid protein known as GATA1s. These arise by either alternative splicing or use of alternate translational start sites from the full-length transcript. In TAM and ML-DS. GATA1 mutations abrogate GATA1fl production, leading to exclusive production of GATA1s. The morphology and immunophenotypic profile of TAM and ML-DS blasts8-11  are not absolutely specific, but can be shared with normal immature blast cells in neonates with DS....

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