| First Author | Hauer J | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 3 | Pages | 544-53 |
| PubMed ID | 21622646 | Mgi Jnum | J:174869 |
| Mgi Id | MGI:5141354 | Doi | 10.1182/blood-2010-09-305383 |
| Citation | Hauer J, et al. (2011) Loss of p19Arf in a Rag1-/- B-cell precursor population initiates acute B-lymphoblastic leukemia. Blood 118(3):544-53 |
| abstractText | In human B-acute lymphoblastic leukemia (B-ALL), RAG1-induced genomic alterations are important for disease progression. However, given that biallelic loss of the RAG1 locus is observed in a subset of cases, RAG1's role in the development of B-ALL remains unclear. We chose a p19Arf(-/-)Rag1(-/-) mouse model to confirm the previously published results concerning the contribution of CDKN2A (p19ARF /INK4a) and RAG1 copy number alterations in precursor B cells to the initiation and/or progression to B-acute lymphoblastic leukemia (B-ALL). In this murine model, we identified a new, Rag1-independent leukemia-initiating mechanism originating from a Sca1(+)CD19(+) precursor cell population and showed that Notch1 expression accelerates the cells' self-renewal capacity in vitro. In human RAG1-deficient BM, a similar CD34(+)CD19(+) population expressed p19ARF. These findings suggest that combined loss of p19Arf and Rag1 results in B-cell precursor leukemia in mice and may contribute to the progression of precursor B-ALL in humans. |
