| First Author | Blaydes SM | Year | 2001 |
| Journal | J Virol | Volume | 75 |
| Issue | 19 | Pages | 9427-34 |
| PubMed ID | 11533205 | Mgi Jnum | J:71729 |
| Mgi Id | MGI:2150612 | Doi | 10.1128/JVI.75.19.9427-9434.2001 |
| Citation | Blaydes SM, et al. (2001) Retroviral integration at the epi1 locus cooperates with nf1 gene loss in the progression to acute myeloid leukemia. J Virol 75(19):9427-34 |
| abstractText | Juvenile myelomonocytic leukemia (JMML) is a disease that occurs in young children and is associated with a high mortality rate. In most patients, JMML has a progressive course leading to death by virtue of infection, bleeding, or progression to acute myeloid leukemia (AML). As it is known that children with neurofibromatosis type 1 syndrome have a markedly increased risk of developing JMML, we have previously developed a mouse model of JMML through reconstitution of lethally irradiated mice with hematopoietic stem cells homozygous for a loss-of-function mutation in the Nf1 gene (D. L. Largaespada, C. I. Brannan, N. A. Jenkins, and N. G. Copeland, Nat. Genet. 12:137-143, 1996). In the course of these experiments, we found that all these genetically identical reconstituted mice developed a JMML-like disorder, but only a subset went on to develop more acute disease. This result strongly suggests that additional genetic lesions are responsible for disease progression to AML. Here, we describe the production of a unique tumor panel, created using the BXH-2 genetic background, for identification of these additional genetic lesions. Using this tumor panel, we have identified a locus, Epi1, which maps 30 to 40 kb downstream of the Myb gene and appears to be the most common site of somatic viral integration in BXH-2 mice. Our findings suggest that proviral integrations at Epi1 cooperate with loss of Nf1 to cause AML. |
