Rescue of murine Gata1s mutant M7 leukemic cells by full-length Gata1

In this project, we studied a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the GATA1 transcription factor (called GATA1s mutation). The model was generated through retroviral insertional mutagenesis in Gata1s mutant fetal liver progenitors. In this study, we analyzed the dependency of these leukemic cells on the Gata1s mutant protein. Here we report Gata1s mutant leukemic cells were dependent on this mutant protein. Introduction of the full-length Gata1 protein to these cells led to their reduced proliferation and increased differentiation along the megakaryocytic lineage. We transduced leukemic cells with Gata1/estrogen receptor fusion cDNA (Gata1-ER) and generated stable cell lines. Addition of beta-estradiol to culture medium led to activation of the full-length Gata1 protein in synchronized leukemic cells. Gene expression profiles were collected at multiple time points.