| First Author | O'Neil J | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 2 | Pages | 781-5 |
| PubMed ID | 16166587 | Mgi Jnum | J:126197 |
| Mgi Id | MGI:3760700 | Doi | 10.1182/blood-2005-06-2553 |
| Citation | O'Neil J, et al. (2006) Activating Notch1 mutations in mouse models of T-ALL. Blood 107(2):781-5 |
| abstractText | Recent studies have demonstrated that most patients with T-cell acute lymphocytic leukemia (T-ALL) have activating mutations in NOTCH1. We sought to determine whether these mutations are also acquired in mouse models of T-ALL. We sequenced the heterodimerization domain and the PEST domain of Notch1 in our mouse model of TAL1-induced leukemia and found that 74% of the tumors harbor activating mutations in Notch1. Cell lines derived from these tumors undergo G(0)/G(1) arrest and apoptosis when treated with a gamma-secretase inhibitor. In addition, we found activating Notch1 mutations in 31% of thymic lymphomas that occur in mice deficient for various combinations of the H2AX, Tp53, and Rag2 genes. Thus, Notch1 mutations are often acquired as a part of the molecular pathogenesis of T-ALLs that develop in mice with known predisposing genetic alterations. |
