| First Author | Swanson PJ | Year | 2004 |
| Journal | J Immunol | Volume | 172 |
| Issue | 11 | Pages | 6684-91 |
| PubMed ID | 15153484 | Mgi Jnum | J:90515 |
| Mgi Id | MGI:3044059 | Doi | 10.4049/jimmunol.172.11.6684 |
| Citation | Swanson PJ, et al. (2004) Fatal acute lymphoblastic leukemia in mice transgenic for B cell-restricted bcl-xL and c-myc. J Immunol 172(11):6684-91 |
| abstractText | Expression of the c-myc gene is frequently dysregulated in malignant tumors and translocations of c-myc into the Ig H chain locus are associated with Burkitt's-type lymphoma. There is indirect evidence that bcl-x, an anti-apoptotic member of the bcl-2 gene family, may also contribute to a variety of B lymphoid tumors. In this study, we show that mice transgenic for both B cell-restricted c-myc and bcl-x(L) developed aggressive, acute leukemias expressing early B lineage and stem cell surface markers. Of interest, the tumor cells proliferated and differentiated down the B cell developmental pathway following in vitro treatment with IL-7. Analysis of sorted leukemic cells from spleen indicated constitutive expression of sterile micro and kappa transcripts in combination with evidence for D-J(H) DNA rearrangements. Several B cell-specific genes were either not expressed or were expressed at low levels in primary tumor cells and were induced following culture with IL-7. IL-7 also increased V-Jkappa and V-DJ(H) rearrangements. These data demonstrate oncogenic synergy between c-myc and bcl-x(L) in a new mouse model for acute lymphoblastic leukemia. Tumors in these animals target an early stage in B cell development characterized by the expression of both B lineage and stem cell genes. |
