Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

Published online

Journal Article

The ecotropic virus integration site 1 (EVI1) transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.

Full Text

Duke Authors

Cited Authors

  • Glass, C; Wuertzer, C; Cui, X; Bi, Y; Davuluri, R; Xiao, Y-Y; Wilson, M; Owens, K; Zhang, Y; Perkins, A

Published Date

  • 2013

Published In

Volume / Issue

  • 8 / 6

Start / End Page

  • e67134 -

PubMed ID

  • 23826213

Pubmed Central ID

  • 23826213

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0067134

Language

  • eng

Conference Location

  • United States