Molecular, biologic, and clinical data, such as the study by Gamis et al,¹  indicate that transient myeloproliferative disorder (TMD) and Down syndrome–associated acute myeloid leukemia (ML-DS) are initiated before birth when fetal liver hematopoietic stem and/or progenitor cells trisomic for chromosome 21 acquire GATA1 mutations. TMD usually presents around birth with a spectrum of clinical features from life-threatening hepatic fibrosis to asymptomatic leukocytosis. Although most cases of TMD spontaneously and permanently remit by the age of 6 months, in 15% to 30% of cases additional genetic events lead to further expansion of the trisomic GATA1-containing clone(s) resulting in ML-DS before the age of 5 years.