| First Author | Schubbert S | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 23 | Pages | 7048-59 |
| PubMed ID | 25287161 | Mgi Jnum | J:217184 |
| Mgi Id | MGI:5613288 | Doi | 10.1158/0008-5472.CAN-14-1470 |
| Citation | Schubbert S, et al. (2014) Targeting the MYC and PI3K pathways eliminates leukemia-initiating cells in T-cell acute lymphoblastic leukemia. Cancer Res 74(23):7048-59 |
| abstractText | Disease relapse remains the major clinical challenge in treating T-cell acute lymphoblastic leukemia (T-ALL), particularly those with PTEN loss. We hypothesized that leukemia-initiating cells (LIC) are responsible for T-ALL development and treatment relapse. In this study, we used a genetically engineered mouse model of Pten(-/-) T-ALL with defined blast and LIC-enriched cell populations to demonstrate that LICs are responsible for therapeutic resistance. Unlike acute and chronic myelogenous leukemia, LICs in T-ALL were actively cycling, were distinct biologically, and responded differently to targeted therapies in comparison with their differentiated blast cell progeny. Notably, we found that T-ALL LICs could be eliminated by cotargeting the deregulated pathways driven by PI3K and Myc, which are altered commonly in human T-ALL and are associated with LIC formation. Our findings define critical events that may be targeted to eliminate LICs in T-ALL as a new strategy to treat the most aggressive relapsed forms of this disease. |
