High-Level IGF1R Expression is Required for Leukemia-Initiating Cell Activity in T-ALL and is Supported by Notch Signaling
DSpace/Manakin Repository
High-Level IGF1R Expression is Required for Leukemia-Initiating Cell Activity in T-ALL and is Supported by Notch Signaling
| Title: | High-Level IGF1R Expression is Required for Leukemia-Initiating Cell Activity in T-ALL and is Supported by Notch Signaling |
| Author: |
Medyouf, Hind; Gusscott, Samuel; Wai, Carol; Nemirovsky, Oksana; Trumpp, Andreas; Pflumio, Francoise; Carboni, Joan; Gottardis, Marco; Pollak, Michael; Holzenberger, Martin; Weng, Andrew P.; Wang, Hongfang; Tseng, Jen-Chieh; Kung, Andrew Li-Jen; Aster, Jon Christopher
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Medyouf, Hind, Samuel Gusscott, Hongfang Wang, Jen-Chieh Tseng, Carol Wai, Oksana Nemirovsky, Andreas Trumpp, et al. 2011. High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling. Journal of Experimental Medicine 208(9): 1809-1822. |
| Full Text & Related Files: |
3171095.pdf (2.976Mb; PDF) 
|
| Abstract: | T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer of immature T cells that often shows aberrant activation of Notch1 and PI3K–Akt pathways. Although mutations that activate PI3K–Akt signaling have previously been identified, the relative contribution of growth factor-dependent activation is unclear. We show here that pharmacologic inhibition or genetic deletion of insulin-like growth factor 1 receptor (IGF1R) blocks the growth and viability of T-ALL cells, whereas moderate diminution of IGF1R signaling compromises leukemia-initiating cell (LIC) activity as defined by transplantability in syngeneic/congenic secondary recipients. Furthermore, IGF1R is a Notch1 target, and Notch1 signaling is required to maintain IGF1R expression at high levels in T-ALL cells. These findings suggest effects of Notch on LIC activity may be mediated in part by enhancing the responsiveness of T-ALL cells to ambient growth factors, and provide strong rationale for use of IGF1R inhibitors to improve initial response to therapy and to achieve long-term cure of patients with T-ALL. |
| Published Version: | doi:10.1084/jem.20110121 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171095/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:8615964 |
This item appears in the following Collection(s)
-
HMS Scholarly Articles [4046]
Contact administrator regarding this item (to report mistakes or request changes)
