| First Author | Dadi S | Year | 2012 |
| Journal | Cancer Cell | Volume | 21 |
| Issue | 4 | Pages | 563-76 |
| PubMed ID | 22516263 | Mgi Jnum | J:186201 |
| Mgi Id | MGI:5431184 | Doi | 10.1016/j.ccr.2012.02.013 |
| Citation | Dadi S, et al. (2012) TLX homeodomain oncogenes mediate T cell maturation arrest in T-ALL via interaction with ETS1 and suppression of TCRalpha gene expression. Cancer Cell 21(4):563-76 |
| abstractText | Acute lymphoblastic leukemias (ALLs) are characterized by multistep oncogenic processes leading to cell-differentiation arrest and proliferation. Specific abrogation of maturation blockage constitutes a promising therapeutic option in cancer, which requires precise understanding of the underlying molecular mechanisms. We show that the cortical thymic maturation arrest in T-lineage ALLs that overexpress TLX1 or TLX3 is due to binding of TLX1/TLX3 to ETS1, leading to repression of T cell receptor (TCR) alpha enhanceosome activity and blocked TCR-Jalpha rearrangement. TLX1/TLX3 abrogation or enforced TCRalphabeta expression leads to TCRalpha rearrangement and apoptosis. Importantly, the autoextinction of clones carrying TCRalpha-driven TLX1 expression supports TLX "addiction" in TLX-positive leukemias and provides further rationale for targeted therapy based on disruption of TLX1/TLX3. |
