Reprogramming stem cells could help prevent cancer post radiation. A program that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever. A University of Colorado Cancer Center study showed that this method is one of the ways to get rid of such stem cells.
The study also showed that this same safeguard of "programmed mediocrity" that weeds out stem cells damaged by radiation allows blood cancers to grow in cases when the full body is irradiated. And by reprogramming this safeguard, it was possible to prevent cancer in the aftermath of full body radiation.
AdvertisementJames DeGregori, PhD, the paper's senior author, who along with his colleagues explored the effects of full body radiation on the blood stem cells of mice, said that the body didn't evolve to deal with leaking nuclear reactors and CT scans. It evolved to deal with only a few cells at a time receiving dangerous doses of radiation or other insults to their DNA.
DeGregori found that mutations and other genetic alterations resulting in inhibition of the C/EBPA gene were associated with acute myeloid leukemia in humans. Thus, it wasn't mutations caused by radiation but a blood system re-engineered by faulty stem cells that created cancer risk in people who had experienced radiation.
The studies show that by activating a stem cell maintenance pathway, it was possible to keep it from happening. Even months after irradiation, artificially activating the NOTCH signaling pathway of irradiated HSCs lets them act "stemmy" again - restarting the blood cell assembly line in these HSCs that would have otherwise differentiated in response to radiation.
When DeGregori, Fleenor and colleagues activated NOTCH in previously irradiated HSCs, it kept the population of dangerous, C/EBPA cells at bay. Competition from non-C/EBPA-mutant stem cells, with their fitness restored by NOTCH activation, meant that there was no evolutionary space for C/EBPA-mutant stem cells.
The study is published in the journal Stem Cells.