News | December 31, 2014

Reprogramming Stem Cells May Prevent Cancer After Radiation

Program can help the body make stem cells differentiate into other cells

December 31, 2014 — A University of Colorado Cancer Center study published in the journal Stem Cells shows that one way the body has evolved to get rid of faulty stem cells is a “program” that makes stem cells damaged by radiation differentiate into other cells that can no longer survive forever.

The study also shows 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. By reprogramming this safeguard, cancer may be preventable in the aftermath of full body radiation.

James DeGregori, Ph.D., investigator at the CU Cancer Center, professor of Biochemistry and Molecular Genetics at the CU School of Medicine and the paper’s senior author; doctoral student Courtney Fleenor and colleagues 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. Stem cells with a very specific mutation were able to disobey the instruction to differentiate and retain their stemness. 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. In this way, the blood system transitioned from C/EBPA+ cells to primarily C/EBPA- cells.

Mutations and other genetic alterations resulting in inhibition of the C/EBPA gene are associated with acute myeloid leukemia in humans. Thus, it’s not mutations caused by radiation but a blood system reengineered by faulty stem cells that creates cancer risk in people who have experienced radiation.

“It’s about evolution driven by natural selection,” DeGregori says. “In a healthy blood system, healthy stem cells out-compete stem cells that happen to have the C/EBPA mutation. 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.”

These studies explain why radiation makes hematopoietic stem cells (HSCs) differentiate and show that by activating a stem cell maintenance pathway this can be prevented. 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.

“If I were working in a situation in which I was likely to experience full-body radiation, I would freeze a bunch of my HSCs,” DeGregori says, explaining that an infusion of healthy HSCs after radiation exposure would likely allow the healthy blood system to out-compete the radiation-exposed HSC with their “programmed mediocrity” (increased differentiation) and even HSC with cancer-causing mutations. “But there’s also hope that in the future, we could offer drugs that would restore the fitness of stem cells left over after radiation.”

For more information: www.ucdenver.edu/academics/colleges/medicalschool/centers/cancercenter/P...

Related Content

ZON-PTC in Clinical Use With RayStation 8B and Hyperscan
News | Treatment Planning | March 19, 2019
Zuid-Oost Nederland Protonen Therapie Centrum (ZON-PTC), Maastricht, Netherlands, recently treated its first patient...
Older Biologic Age Linked to Elevated Breast Cancer Risk
News | Women's Health | March 19, 2019
Biologic age, a DNA-based estimate of a person’s age, is associated with future development of breast cancer, according...
HeartFlow Analysis Successfully Stratifies Heart Disease Patients at One Year
News | CT Angiography (CTA) | March 19, 2019
Late-breaking results confirm the HeartFlow FFRct (fractional flow reserve computed tomography) Analysis enables...
PET Scans Show Biomarkers Could Spare Some Breast Cancer Patients from Chemotherapy
News | PET Imaging | March 18, 2019
A new study positron emission tomography (PET) scans has identified a biomarker that may accurately predict which...
SyncVision iFR Co-registration from Philips Healthcare maps iFR pressure readings onto angiogram.

SyncVision iFR Co-registration from Philips Healthcare maps iFR pressure readings onto angiogram. Results from an international study presented at #ACC19 show that pressure readings in coronary arteries may identify locations of stenoses remaining after cardiac cath interventions.

Feature | Cardiac Imaging | March 18, 2019 | By Greg Freiherr
As many as one in four patients who undergo cath lab interventions can benefit from a technology that identifies the
Non-Contrast MRI Effective in Monitoring MS Patients
News | Neuro Imaging | March 18, 2019
Brain magnetic resonance imaging (MRI) without contrast agent is just as effective as the contrast-enhanced approach...
Bay Labs Announces New Data on EchoGPS, AutoEF AI Software at ACC.19
News | Cardiovascular Ultrasound | March 15, 2019
Artificial intelligence (AI) company Bay Labs announced the presentation of two studies assessing performance of the...
What to Expect from the Proton Therapy Market in 2019-2020
News | Proton Therapy | March 13, 2019
The number of new particle therapy rooms ordered worldwide dropped by almost 20 percent in 2018, according to a new...
CT, Mammograms Offer Clues to Preventing Heart Problems After Cancer Treatment
News | Cardio-oncology | March 13, 2019
An imaging procedure commonly performed before starting cancer treatment can provide valuable clues about a patient's...
Iron Measurements With MRI Reveal Stroke's Impact on Brain

Images show illustrative examples of visual R2? modifications within substantia nigra (SN) at baseline (24-72 h) and follow-up (1 y) in striatum (participants 1 and 2) and control groups (participants 3 and 4). Image courtesy of the Radiological Society of North America (RSNA).

News | Stroke | March 12, 2019
March 12, 2019 — A simple ...