In the last decade, the question regarding whether all cells within a tumor are equal or whether some cancer cells are more powerful has been highly investigated in experimental models. Research published recently in Nature Medicine, however, centers on patients and shows that acute myeloid leukemia (AML) contains rare cells with stem cell properties, called leukemia stem cells (LSC). These LSCs better predict clinical outcome than the majority of AML cells, thus establishing for the first time that LSCs are significant in patients.
“Even though LSCs are like a needle in a haystack, their unique properties influence whether AML will respond to therapy or whether the disease comes back. This means that future efforts to prevent the disease from recurring and improving overall patient survival must consider ways to target LSCs to ensure they are killed,” says principal investigator John Dick, who holds a Canada Research Chair in Stem Cell Biology and is a senior scientist at the McEwen Centre for Regenerative Medicine and the Ontario Cancer Institute, Princess Margaret Hospital. Dr Dick pioneered the cancer stem cell field by identifying leukemia stem cells in 1994 and colon cancer stem cells in 2007.
Dr Dick’s international research team sorted, analyzed, and compared healthy stem cells, leukemia stem cells, and clinical data in order to reveal a signature that was common to both normal and LSCs. The researchers demonstrated that the patents’ course of disease could be accurately predicted by the set of genes. Patients that highly expressed the stem cell signature had much shorter survival compared to those patients that had low expression of the signature.
Furthermore, the genes within the stem cell signature provide new drug targets that could be used to eliminate LSCs. These genes also represent possible AML biomarkers with the potential for identifying patients who might benefit from more aggressive therapy. In the long term, this information could help personalize cancer therapy. Physicians could get the right drug to the right patient, as opposed to a “one-size-fits-all” approach of treating patients identically.
“Although our research was on AML, our findings that LSCs are real and relevant in patients set the entire cancer stem cell field on a firmer footing. Our approach could be used as a template to test the clinical importance of cancer stem cells from solid tumors and other forms of leukemia,” says Dr Dick, who works out of University Health Network’s Ontario Cancer Institute, where stem cell science began 50 years ago.
Source: University Health Network