In an advancement that may change how doctors predict and treat certain blood cancers, researchers at Huntsman Cancer Institute at the University of Utah have identified a gene variant commonly found in high-altitude Andean populations that appears to influence disease severity and treatment response.
Dr. Josef Prchal is an investigator at Huntsman Cancer Institute and the Charles A. Nugent, MD, and Margaret Nugent Endowed Professor of Medicine/Hematology at the University of Utah.
The findings, presented during the late-breaking abstract sessions at the 66th Annual Meeting and Exposition of the American Society of Hematology, are the result of work led by Dr. Jihyun Song, an investigator at Huntsman Cancer Institute and assistant professor in the Division of Hematology & Hematologic Malignancies, and Dr. Josef Prchal, an investigator at Huntsman Cancer Institute and the Charles A. Nugent, MD, and Margaret Nugent Endowed Professor in Medicine/Hematology at the University of Utah. Their abstract was one of only six chosen this year for a late-breaking presentation.
“This is the first study to connect genetic traits associated with life at high altitudes to outcomes in blood cancers,” said Song. “Our results suggest that this variant of the NFKB1 gene may help predict a patient’s level of inflammation and the likelihood of responding well to treatment.”
The work builds on an extensive genomic study of the Aymara people, an indigenous group native to the Andes Mountains. NFKB1 typically triggers inflammation, which can, over time, promote abnormal cell growth and cancer. Approximately 90% of the Aymara carry the enriched variant of NFKB1, but it also appears in about 30% of people of European, Hispanic, and Asian heritage.
With blood cancers — diseases often marked by high inflammation — patients carrying this variant had lower inflammation levels and better responses to treatment. Researchers believe the gene’s protective role may have evolved as an adaptation to high-altitude conditions, where inflammation-related complications such as blood clots can be more common.
Dr. Prchal, an expert in polycythemia vera, essential thrombocythemia, and other myeloproliferative neoplasms, noted that the discovery arose from evolutionary research rather than cancer studies. “We initially found this pathway by studying high-altitude adaptation,” he said. “Once we recognized its influence on inflammation, it opened the door to applying this knowledge to our blood cancer patients.”
Myeloproliferative neoplasms cause the bone marrow to overproduce blood cells, raising the risk of clots and potentially progressing into more severe conditions like myelofibrosis and leukemia. According to Song and Prchal, about 30% of patients with polycythemia vera and essential thrombocythemia who carry the Andean variant achieve complete remission more often, potentially leading to better long-term outcomes.
The team hopes these insights could guide the development of new therapies that mimic the variant’s beneficial effects. The research was supported by the National Institutes of Health/National Cancer Institute, the MPN Foundation, the Brown Foundation, and Huntsman Cancer Foundation.
