Children with Down syndrome have a high risk of developing acute megakaryoblastic leukemia (AMKL) but the genetic mechanisms involved have remained elusive. In August 12 advanced online Nature Genetics, Joshua Wechsler and colleagues at the University of Chicago, Illinois, US, show that loss of the full length GATA1 constitutes one step in the pathogenesis of AMKL in Down syndrome (Nat Genet 2002, DOI:10.1038/ng955).

Wechsler et al. observed that leukaemic cells from every individual with DS-AMKL they examined contained mutations in GATA1 on the X chromosome — GATA1 encodes the essential hematopoietic transcription factor GATA1 (GATA binding protein 1 or globin transcription factor 1). These mutations resulted in the introduction of a premature stop codon in the gene sequence and prevented synthesis of full-length GATA1, but not synthesis of a shorter variant that is initiated downstream. In addition, they observed that the shorter GATA1 protein has a...