Formation of atypical, hyperproliferating eosinophilic precursors by overexpression of GATA1s

Transcription factor GATA1 is essential for the development of megakaryocytes, erythrocytes and eosinophils. GATA1-mutations (GATA1s) are associated with Down syndrome (DS) transient leukemia (TL). Here, we report a series of DS-TL patients with eosinophilia that carry the same GATA1s-mutation in the sorted eosinophils as in the leukemic blasts. To explore the effect of GATA1s on myeloid differentiation in the human context, we established a lentiviral vector system for simultaneous downregulation of endogenous GATA1 and ectopic expression of GATA1s/GATA1 in hematopoietic stem and progenitor cells (HSPCs) from h…