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Publication : Ablation of Fbxw7 eliminates leukemia-initiating cells by preventing quiescence.

First Author  Takeishi S Year  2013
Journal  Cancer Cell Volume  23
Issue  3 Pages  347-61
PubMed ID  23518349 Mgi Jnum  J:197046
Mgi Id  MGI:5490695 Doi  10.1016/j.ccr.2013.01.026
Citation  Takeishi S, et al. (2013) Ablation of Fbxw7 eliminates leukemia-initiating cells by preventing quiescence. Cancer Cell 23(3):347-61
abstractText  Imatinib eradicates dividing progenitor cells of chronic myeloid leukemia (CML) but does not effectively target nondividing leukemia-initiating cells (LICs); thus, the disease often relapse after its discontinuation. We now show that Fbxw7 plays a pivotal role in maintenance of quiescence in LICs of CML by reducing the level of c-Myc. Abrogation of quiescence in LICs by Fbxw7 ablation increased their sensitivity to imatinib, and the combination of Fbxw7 ablation with imatinib treatment resulted in a greater depletion of LICs than of normal hematopoietic stem cells in mice. Purging of LICs by targeting Fbxw7 to interrupt their quiescence and subsequent treatment with imatinib may thus provide the basis for a promising therapeutic approach to CML.
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