Genome-scale expression and transcription factor binding profiles reveal therapeutic targets in transgenic ERG myeloid leukemia

ABSTRACT: Here we show that pan-haematopoietic ERG expression driven by the Vav promoter induces an early progenitor myeloid leukemia in transgenic mice. Integrated genome-scale analysis of gene expression and ERG binding profiles revealed that ERG activates a transcriptional program similar to human AML stem/progenitor cells and human AML with high ERG expression. We further show that ERG induces expression of the Pim1 kinase oncogene through a novel enhancer element validated in transgenic mice, and Pim1 inhibition disrupts growth and induces apoptosis of ERG-driven leukemic cells. In addition, ERG indirectly induces the RAS pathway and direct RAS inhibition by a RAS inhibitor blocks growth of leukemia cells in vitro and in vivo. Thus, integrative genomic analysis of transgenic ERG leukemias reve

ORGANISM(S): Mus musculus

SUBMITTER: Rebecca Hannah 

PROVIDER: E-GEOD-46554 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress