Developmental stage-specific interplay between GATA1 and IGF signaling during fetal hematopoiesis and leukemogenesis

Fetal and adult hematopoiesis are distinct. Signaling pathways and their coordination with lineage-specific transcription during fetal hematopoiesis and their subversion during leukemogenesis are poorly understood. Down syndrome acute megakaryoblastic leukemia (AMKL) is characterized by a triad of fetal origin, mutated GATA1 (GATA1s), and trisomy 21, providing a unique model system to address these issues. We used a cross-species integrated genomic approach to understand how developmental specificity is achieved in DS-AMKL and demonstrate overactivity of IGF signaling in both a DS-AMKL mouse-model -generated thr…