| First Author | Harb JG | Year | 2008 |
| Journal | Blood | Volume | 111 |
| Issue | 7 | Pages | 3760-9 |
| PubMed ID | 18216295 | Mgi Jnum | J:133520 |
| Mgi Id | MGI:3778735 | Doi | 10.1182/blood-2007-08-108803 |
| Citation | Harb JG, et al. (2008) Loss of Bcl-x in Ph+ B-ALL increases cellular proliferation and does not inhibit leukemogenesis. Blood 111(7):3760-9 |
| abstractText | The kinase inhibitors imatinib mesylate and dasatinib are the preferred treatment for Philadelphia chromosome-positive (Ph+) leukemias, and they are highly successful in the chronic phase of chronic myeloid leukemia (CML). However, they are not efficient in Ph+ B-cell acute lymphoblastic leukemia (B-ALL). Ph+ leukemia cells are highly resistant to apoptosis, and evidence from cell lines and primary cells suggest Bcl-xL as a critical mediator of resistance to apoptosis: however, this concept has never been rigorously tested in an animal model. To clarify the role of Bcl-xL in Ph+ B-ALL, we generated 2 mouse models. In the first model, Ph+ B-ALL and loss of Bcl-xL expression are coinduced; in the second model, leukemia is induced with expression of Bcl-xL protein well above the levels found in wild-type lymphoblasts. Deletion of Bcl-xL did not inhibit leukemogenesis or affect apoptosis, but increased cellular proliferation. Consistent with this result, overexpression of Bcl-xL led to decreased cellular proliferation. These models reveal an unexpected role for Bcl-xL in cell-cycle entry and the proliferation of tumor cells. |
