University of Colorado researchers reveal a novel metabolic weakness in MDS stem cells, paving the way for more precise cancer treatments.
Researchers at the University of Colorado Anschutz Cancer Center have identified a significant metabolic weakness in the stem cells linked to high-risk myelodysplastic syndromes (MDS), a class of aggressive blood cancers. This discovery, reported in Blood Cancer Discovery, could lead to targeted therapies aimed at these cancerous stem cells, offering hope for better patient outcomes.
The study reveals that MDS stem cells rely disproportionately on nicotinamide adenine dinucleotide (NAD), a critical molecule involved in cellular energy production. Disrupting the pathways that maintain NAD levels selectively weakened these malignant cells, while healthier blood-forming stem cells demonstrated greater adaptability.
According to Dr. Eric M. Pietras, an associate professor in Hematology and co-lead author of the study, “What we found is that these cells actually use energy in different ways than normal stem cells do. They were relying on a specific set of proteins and processes that created a vulnerability we could potentially target.”
Myelodysplastic syndromes hinder the bone marrow's capacity to generate healthy blood cells, leading to severe anemia and frequent infections, with high-risk cases further escalating to acute myeloid leukemia (AML). In the U.S., between 10,000 to 20,000 new MDS diagnoses are made each year, predominantly in older populations.
The research team aimed to distinguish the biological features between cancerous stem cells and their healthy counterparts. Their experiments highlighted the heightened dependence of MDS stem cells on the NAD salvage pathway—a recycling mechanism essential for maintaining NAD levels. Within this pathway, the enzyme nicotinamide phosphoribosyltransferase (NAMPT) emerged as a promising therapeutic target.
Dr. Pietras emphasized this dependency, stating, “These cells had developed a much greater need for this resource. They appear to use NAD at a much higher rate than normal cells, which creates a vulnerability that we can exploit with new types of drugs.”
An "Energy Addiction" to Exploit
This pronounced reliance on NAD is described by the researchers as an "energy addiction." Healthy blood stem cells possess the flexibility to adapt their energy production methods under stress conditions, but MDS stem cells lack this adaptability, making them more susceptible to targeted interventions.
When researchers inhibited NAMPT, they noted a significant drop in NAD levels among cancer stem cells, inducing an energy crisis that selectively impeded the malignant cells without substantially affecting normal blood-forming stem cells, which managed to adjust more effectively.
Experiments conducted with patient-derived MDS cells and animal models demonstrated that tampering with NAD metabolism effectively reduced the number of disease-driving stem cells. Moving forward, the researchers plan to explore drugs that target NAMPT through clinical trials involving patients afflicted with MDS and similar blood disorders.
“Our goal is to identify approaches that make these complex diseases more treatable by finding the differences between cancer cells and normal cells,” Dr. Pietras noted. “If we can understand those differences, we can begin to develop therapies that are more precise and more effective for patients.”
Co-leading the study alongside Dr. Pietras, Dr. Craig T. Jordan contributed to extensive laboratory research directed by Dr. Sweta B. Patel, in collaboration with additional researchers from the University of Colorado Anschutz, including Angelo D'Alessandro and Julie Reisz Haines, among external partners.
The study received backing from several organizations, including the National Institutes of Health and the Edward P. Evans Foundation, underscoring a collaborative effort to advance blood cancer research.
Source: Materials provided by University of Colorado Anschutz. Content may be edited for style and length.
Don’t Miss: Saturn, Halley’s Comet Meteors and the Seven Sisters Light Up October
Scientists Discover 5 Hidden Forms of a Liver Disease Affecting 30% of Adults
Could Vitamin C Help Stop Leukemia Before It Starts?
Study Finds Natural Dairy Trans Fats Behave Very Differently From Industrial Fats
Stay informed with ScienceDaily's free email newsletter, updated daily and weekly. Or view our many newsfeeds in your RSS reader:
Keep up to date with the latest news from ScienceDaily via social networks:
Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Discussion
Sign in to join the discussion.