This suggests the disturbance of distinct signaling pathways due to enhanced transcription of specific genes in DS can be potentially attributed to the gene dosage effect of HMGN1. The concept that increased gene dosage of HMGN1 is necessary and sufficient for the induction of DS-specific ALL suggests the possibility that HMGN1 triplication can be detrimental in other DS-related phenotypes observed in different systems. This evidence concerns the gene HMGN1 and acute lymphoblastic leukemia.