| First Author | Bornschein S | Year | 2018 |
| Journal | Leukemia | Volume | 32 |
| Issue | 4 | Pages | 941-951 |
| PubMed ID | 29151585 | Mgi Jnum | J:265705 |
| Mgi Id | MGI:6149116 | Doi | 10.1038/leu.2017.328 |
| Citation | Bornschein S, et al. (2018) Defining the molecular basis of oncogenic cooperation between TAL1 expression and Pten deletion in T-ALL using a novel pro-T-cell model system. Leukemia 32(4):941-951 |
| abstractText | T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple mutations combined with the ectopic expression of transcription factors in developing T cells. However, the molecular basis underlying cooperation between transcription factor expression and additional oncogenic mutations in driving T-ALL has been difficult to assess due to limited robust T-cell model systems. Here we utilize a new ex vivo pro-T-cell model to study oncogenic cooperation. Using a systems biological approach we first dissect the pro-T-cell signaling network driven by interleukin-7, stem cell factor and Notch1 and identify key downstream Akt, Stat, E2f and Myc genetic signaling networks. Next, this pro-T-cell system was used to demonstrate that ectopic expression of the TAL1 transcription factor and Pten deletion are bona-fide cooperating events resulting in an increased stem cell signature, upregulation of a specific E2f signaling network and metabolic reprogramming with higher influx of glucose carbons into the tricarboxylic acid cycle. This ex vivo pro-T-cell system thereby provides a powerful new model system to investigate how normal T-cell signaling networks are perturbed and/or hijacked by different oncogenic events found in T-ALL. |
