| First Author | Kaveri D | Year | 2013 |
| Journal | Blood | Volume | 122 |
| Issue | 5 | Pages | 694-704 |
| PubMed ID | 23801632 | Mgi Jnum | J:202272 |
| Mgi Id | MGI:5517762 | Doi | 10.1182/blood-2012-12-471904 |
| Citation | Kaveri D, et al. (2013) beta-Catenin activation synergizes with Pten loss and Myc overexpression in Notch-independent T-ALL. Blood 122(5):694-704 |
| abstractText | Wnt signaling is important for T-cell differentiation at the early CD4(-)CD8(-) stage and is subsequently downregulated with maturation. To assess the importance of this downregulation, we generated a mouse line (R26-betacat) in which high levels of active beta-catenin are maintained throughout T-cell development. Young R26-betacat mice show a differentiation block at the CD4(+)CD8(+) double-positive (DP) stage. These DP cells exhibit impaired apoptosis upon irradiation or dexamethasone treatment. All R26-betacat mice develop T-cell leukemias at 5 to 6 months of age. R26-betacat leukemias remain dependent on beta-catenin function but lack Notch pathway activation. They exhibit recurrent secondary genomic rearrangements that lead to Myc overexpression and loss of Pten activity. Because beta-catenin activation and Myc translocations were previously found in murine T-cell acute lymphoblastic leukemias (T-ALLs) deficient for Pten, our results suggest that activation of the canonical Wnt pathway is associated with a subtype of Notch-independent T-ALLs that bear Myc gene rearrangements and Pten mutations. |
