Refining the model of dosage imbalance in TAM/ML-DS. From this study, the impact of trisomy 21 on TAM/ML-DS pathogenesis has been refined from the “classical” model (gene dosage effect, left panel) to a “new” model in which the combination of 3 chromosome 21 and a disequilibrium of the RUNX1A/RUNX1C transcripts promotes myeloid leukemia in children with DS (right panel). Professional illustration by Somersault18:24.