Biologic and experimental variation of measured cancer stem cells

Whereas it has become clear that measured stem cell frequencies in tumors greatly depend on the assay system used, the research focus now shifts towards identification of the biologic variability of cancer stem cells in different disease subsets. In a recent study we quantified the frequency and in vitro expansion potential of leukemia initiating cells in a murine model of acute myeloid leukemia driven either by retroviral overexpression of MN1 and a control vector, or by MN1 and a HOX gene through limiting dilution transplantation assays in syngeneic mice. Both leukemia-initiating cell frequency and expansion potential were increased by over two orders of magnitude in the two-oncogene compared to the one-oncogene model, documenting the functional heterogeneity of leukemia-initiating cells. Loss-of-function studies showed that STAT5b and STAT1 are critical for the enhanced self-renewal activity. Here we discuss implications of our findings and potential sources of experimental variability of measured leukemia or cancer stem cell frequencies.