| First Author | Thomas EK | Year | 2007 |
| Journal | Cancer Cell | Volume | 12 |
| Issue | 5 | Pages | 467-78 |
| PubMed ID | 17996650 | Mgi Jnum | J:127321 |
| Mgi Id | MGI:3763570 | Doi | 10.1016/j.ccr.2007.10.015 |
| Citation | Thomas EK, et al. (2007) Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease. Cancer Cell 12(5):467-78 |
| abstractText | Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) initiated by expression of the p210-BCR-ABL fusion protein. We demonstrate in a murine model of p210-BCR-ABL-induced MPD that gene targeting of Rac1 and Rac2 significantly delays or abrogates disease development. Attenuation of the disease phenotype is associated with severely diminished p210-BCR-ABL-induced downstream signaling in primary hematopoietic cells. We utilize NSC23766, a small molecule antagonist of Rac activation, to validate biochemically and functionally Rac as a molecular target in both a relevant animal model and in primary human CML cells in vitro and in a xenograft model in vivo, including in Imatinib-resistant p210-BCR-ABL disease. These data demonstrate that Rac is an additional therapeutic target in p210-BCR-ABL-mediated MPD. |
