To detect cancer stem cells may be explained by a context-dependent phenotype of those cells, as supported by evidence from coinjection experiments of stromal and cancer cells. In these studies, the efficiency of transplantation of putative cancer stem cells was higher when stromal cells were co-injected as compared to injection of cancer stem cells alone. This data suggests that the PI-103 ability of cells to initiate neoplastic growth may not only depend on the severity of immunodeficiency of assay mice, but also on the microenvironmental context of these cells. The phenotypic plasticity of stem cells has been a topic attracting great interest. Studies of cells in the central nervous system, for instance, have shown that certain extracellular signals can induce oligodendrocyte precursor cells to dedifferentiate into multipotential neural stem cells. These extracellular signals are provided through exposure to fetal calf serum and certain cytokines, including some bone morphogenic proteins, as well as basic fibroblast growth factor, and cause many purified oligodendrocyte precursors to revert to a state that resembles that of multipotential neural stem cells. Similarly, a study in which mature astrocytes were exposed to transforming growth factor a demonstrated that a single extracellular factor is sufficient to induce differentiated cells of the central nervous system to regress into a stem-like cell stage. This observed plasticity of normal tissue stem cells has implications for tissue organization in general, and the view of rigid differentiation hierarchies of cells must be revised in light of these findings. Observations parallel to those observing a dedifferentiation potential of normal cells have also been made with regard to cancer cells. A recent study identified signaling within the perivascular niche as a driving force for tumor cells to acquire stem cell characteristics. In this study, nitric oxide was shown to activate Notch signaling via cGMP and PKG in a subset of glioma cells resulting in acquisition of the side population phenotype and increased neurosphere and tumor formation. These alterations occurred within as little as two hours of treatment and had long-term effects on the phenotype generally associated with stem cell character. This plasticity of tumor stem cells may also apply to liquid tumors, as it was recently shown that leukemia-initiating cells in AML patients harboring mutations in nucleophosmin can reside in the CD34+ as well as CD34- fraction. The ability of committed cancer progenitors to dedifferentiate to a stem-like state has important implications for the dynamics of tumor progression and the response to therapy. In this paper, we design a novel mathematical model to quantify the effects of the dedifferentiation rate on disease outcome.