Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE62144
PROVIDER: PRJNA263272 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Development of gene expression signatures for ETS1 knockdown in the ALL-SIL cell line.
| PRJNA263271 | ENA
Project description:Development of gene expression signatures for RUNX1 knockdown in the ALL-SIL cell line.
| PRJNA263273 | ENA
Project description:Development of gene expression signatures for JQ1 treatment of the ALL-SIL cell line.
| PRJNA263274 | ENA
Project description:Development of gene expression signatures for GSI treatment of the ALL-SIL cell line.
| PRJNA289235 | ENA
Project description:PolyA+ RNA-seq in ALL-SIL upon TLX1 knockdown
| PRJNA434171 | ENA
Project description:Total RNA-seq in ALL-SIL upon TLX1 knockdown
| PRJNA434175 | ENA
Project description:The T-cell leukemia homeobox 1 (TLX1, HOX11) transcription factor is critically involved in the multistep pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and often cooperates with NOTCH1 activation during malignant T-cell transformation. However, the exact molecular mechanisms by which these T-cell specific oncogenes cooperate during transformation remain to be established. Here, we used an integrative genomics approach to show that the oncogenic properties of TLX1 are mediated by genome-wide interference with the ETS1 and RUNX1 transcription factors. Partial disruption of ETS1 and RUNX1 activity by ectopic TLX1 expression in immature thymocytes drives repression of T-cell specific super-enhancers and mediates an unexpected transcriptional antagonism with NOTCH1 signaling. These phenomena coordinately trigger a TLX1 driven pre-leukemic phenotype in human thymic precursor cells, which corresponds with the in vivo thymic regression observed in murine TLX1 tumor models, and creates a strong genetic pressure for acquiring activating NOTCH1 mutations as a prerequisite for full leukemic transformation. In conclusion, our results uncover a functional antagonism between cooperative oncogenes during the earliest phases of tumor development and provide novel insights in the multistep pathogenesis of TLX1 driven human leukemia. Gene expression was measured in the ALL-SIL T-ALL cell line after electroporation with scrambled siRNA and 2 independent TLX1 targetings siRNAs. Cells were collected 24h after treatment. This was performed for 3 replicates.
2015-08-05 | E-GEOD-62141 | biostudies-arrayexpress
Project description:The T-cell leukemia homeobox 1 (TLX1, HOX11) transcription factor is critically involved in the multistep pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and often cooperates with NOTCH1 activation during malignant T-cell transformation. However, the exact molecular mechanisms by which these T-cell specific oncogenes cooperate during transformation remain to be established. Here, we used an integrative genomics approach to show that the oncogenic properties of TLX1 are mediated by genome-wide interference with the ETS1 and RUNX1 transcription factors. Partial disruption of ETS1 and RUNX1 activity by ectopic TLX1 expression in immature thymocytes drives repression of T-cell specific super-enhancers and mediates an unexpected transcriptional antagonism with NOTCH1 signaling. These phenomena coordinately trigger a TLX1 driven pre-leukemic phenotype in human thymic precursor cells, which corresponds with the in vivo thymic regression observed in murine TLX1 tumor models, and creates a strong genetic pressure for acquiring activating NOTCH1 mutations as a prerequisite for full leukemic transformation. In conclusion, our results uncover a functional antagonism between cooperative oncogenes during the earliest phases of tumor development and provide novel insights in the multistep pathogenesis of TLX1 driven human leukemia. ChIP-sequencing data was generated for TLX1 in the T-ALL cell line ALL-SIL.
2015-08-05 | E-GEOD-62264 | biostudies-arrayexpress
Project description:The experiment was designed in order to knock down the expression of TLX1 gene in T-ALL cell line We used microarrays to identify the gene expression signatures associated with TLX1 knock down in ALLSIL
2011-11-08 | GSE33539 | GEO