Growth factor independence 1 (Gfi1) as a new target for leukemia therapy

Using (conditional) Gfi1 knock-out mice we show that ablation of the transcriptional repressor Gfi1 cures mice from lymphoid leukemia and reduces the expansion of primary human T-ALL xenografts in mice. We find that Gfi1 alters the p53 dependent transcriptional activation of a substantial subset of known p53 target genes and thus sets a threshold for cell death. We used Affymetrix mouse Gene-1.0-ST arrays to define the changes in the gene expression pattern of wt or Gfi1-KO thymocytes (Gfi1-fl/fl X MX-CRE, induced by pIpC) that were either untreated (WT, GfiKO thymocytes), irradiated (WT_irr, Gfi1KO_irr), ENU transformed (WT_Tum, Gfi1KO_Tum), or transformed by Notch1-CT and ENU-induced to enhance tumorigenesis (WT_Notch_Tum, Gfi1KO_Notch_Tum). The study should determine how loss of Gfi1 alters the gene expression pattern in irradiated or tumor derived thymocytes