| First Author | Oravecz-Wilson KI | Year | 2009 |
| Journal | Cancer Cell | Volume | 16 |
| Issue | 2 | Pages | 137-48 |
| PubMed ID | 19647224 | Mgi Jnum | J:151974 |
| Mgi Id | MGI:4355644 | Doi | 10.1016/j.ccr.2009.06.007 |
| Citation | Oravecz-Wilson KI, et al. (2009) Persistence of leukemia-initiating cells in a conditional knockin model of an imatinib-responsive myeloproliferative disorder. Cancer Cell 16(2):137-48 |
| abstractText | Despite remarkable responses to the tyrosine kinase inhibitor imatinib, CML patients are rarely cured by this therapy perhaps due to imatinib refractoriness of leukemia-initiating cells (LICs). Evidence for this is limited because of poor engraftment of human CML-LICs in NOD-SCID mice and nonphysiologic expression of oncogenes in retroviral transduction mouse models. To address these challenges, we generated mice bearing conditional knockin alleles of two human oncogenes: HIP1/PDGFbetaR (H/P) and AML1-ETO (A/E). Unlike retroviral transduction, physiologic expression of H/P or A/E individually failed to induce disease, but coexpression of both H/P and A/E led to rapid onset of a fully penetrant, myeloproliferative disorder, indicating cooperativity between these two alleles. Although imatinib dramatically decreased disease burden, LICs persisted, demonstrating imatinib refractoriness of LICs. |
