Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia
| Autor: | Archibald S. Perkins, Xiaohui Cui, Ramana V. Davuluri, Ying Yi Xiao, Yingtao Bi, Michael P Wilson, Yi Zhang, Charles A. Wuertzer, Kristina Owens, Carolyn Glass |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Myeloid
Cellular differentiation Gene Identification and Analysis Hematologic Cancers and Related Disorders Mice 0302 clinical medicine hemic and lymphatic diseases Genetics Regulation of gene expression 0303 health sciences Multidisciplinary Myeloid leukemia Cell Differentiation Hematology 3. Good health DNA-Binding Proteins Gene Expression Regulation Neoplastic Leukemia Leukemia Myeloid Acute medicine.anatomical_structure STAT1 Transcription Factor 030220 oncology & carcinogenesis Medicine Sequence Analysis Signal Transduction Research Article Acute Myeloid Leukemia Science Biology Cell Line Molecular Genetics 03 medical and health sciences Proto-Oncogenes Leukemias medicine Plasminogen Activator Inhibitor 2 Animals Humans 030304 developmental biology Janus Kinases RUNX1T1 Computational Biology CEBPE medicine.disease MDS1 and EVI1 Complex Locus Protein Gene expression profiling Cancer research CCAAT-Enhancer-Binding Proteins Transcriptome Transcription Factors Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 6, p e67134 (2013) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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