Reprogramming stem cells may prevent cancer after radiation

After full body radiation, certain faulty stem cells re-engineer the blood system that creates cancer risk in people which can be prevented by artificially activating a stem cell maintenance pathway, research has found.

"In a healthy blood system, healthy stem cells out-compete stem cells that happen to have the C/EBPA (gene) mutation," said senior author James DeGregori, investigator at University of Colorado Cancer Center.

"But when radiation reduces the heath and robustness (what we call 'fitness') of the stem cell population, the mutated cells that have been there all along are suddenly given the opportunity to take over," DeGregori added.

The study does not just shows why radiation makes hematopoietic stem cells (HSCs) differentiate; it also demonstrates that by activating a stem cell maintenance pathway, it can be kept at bay.

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, the findings showed.

The Notch signaling pathway is an inter-cellular signaling mechanism essential for proper embryonic development.

The researchers explored the effects of full body radiation on the blood stem cells of mice.

In this case, radiation increased the probability that cells in the hematopoietic stem cell system would differentiate.

Only, while most followed this instruction, a few did not. Genetic inhibition of the gene C/EBPA allowed a few stem cells to keep the ability to act as stem cells.

With competition from other, healthy stem cells removed, the stem cells with reduced C/EBPA were able to dominate the blood cell production system.

The study appeared in the journal Stem Cells.