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Publication : Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells.

First Author  Ashton JM Year  2012
Journal  Cell Stem Cell Volume  11
Issue  3 Pages  359-72
PubMed ID  22863534 Mgi Jnum  J:192788
Mgi Id  MGI:5466478 Doi  10.1016/j.stem.2012.05.024
Citation  Ashton JM, et al. (2012) Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells. Cell Stem Cell 11(3):359-72
abstractText  Leukemia stem cells (LSCs) represent a biologically distinct subpopulation of myeloid leukemias, with reduced cell cycle activity and increased resistance to therapeutic challenge. To better characterize key properties of LSCs, we employed a strategy based on identification of genes synergistically dysregulated by cooperating oncogenes. We hypothesized that such genes, termed "cooperation response genes" (CRGs), would represent regulators of LSC growth and survival. Using both a primary mouse model and human leukemia specimens, we show that CRGs comprise genes previously undescribed in leukemia pathogenesis in which multiple pathways modulate the biology of LSCs. In addition, our findings demonstrate that the CRG expression profile can be used as a drug discovery tool for identification of compounds that selectively target the LSC population. We conclude that CRG-based analyses provide a powerful means to characterize the basic biology of LSCs as well as to identify improved methods for therapeutic targeting.
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