Summary
Each year, тИ╝200,000 babies worldwide are born with Down syndrome (DS), owing to constitutional trisomy of chromosome 21 (T21) (1). Children with DS have a markedly increased risk of leukemia, particularly in their first 4 years. Almost 60,000 (30%) will harbor within their blood cells damaging, fetally acquired mutations in the transcription factor gene GATA binding protein 1 (GATA1), which encodes a short GATA1 protein (GATA1s) and triggers the first step in the development of leukemia (2). GATA1 mutations are rare in disomic individuals and virtually never cause leukemia in the absence of T21. Why GATA1 mutations are so frequent in T21 babies and the mechanisms by which a supernumerary chromosome 21 (Hsa21) predisposes to, and cooperates with, genetic events in DS leukemogenesis are not known. On page 179 of this issue, Wagenblast et al. (3) identify Hsa21 microRNAs (miRNAs) that cooperate with GATA1s and map the cellular origin of the leukemia.
