Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL
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ABSTRACT: The TLX1 and TLX3 transcription factor oncogenes play an important role in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL)1,2. Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This Systems Biology analysis defined TLX1 and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, network structure analysis of this hierarchical network identified RUNX1 as an important mediator of TLX1 and TLX3 induced T-ALL, and predicted a tumor suppressor role for RUNX1 in T-cell transformation. Consistent with these results, we identified recurrent somatic loss of function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 atop of an oncogenic transcriptional network controlling leukemia development, demonstrate power of network analysis to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor suppressor gene in T-ALL. This SuperSeries is composed of the following subset Series: GSE33539: Expression data obtained from ALLSIL cell line GSE33540: Expression data obtained from HPBALL cell line GSE33549: Expression data from mouse T-cell lymphomas
ORGANISM(S): Mus musculus
SUBMITTER: Adolfo Ferrando
PROVIDER: E-GEOD-33550 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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