Reposted from Huntsman Cancer Institute.

University of Utah researchers have identified a gene variant found in high-altitude Andean populations that they believe could be a biomarker for predicting the severity of diseases and treatment responses for certain types of blood cancer.

Hematologists Jihyun Song and Josef Prchal, both investigators at Huntsman Cancer Institute, presented their findings in the late-breaking abstract sessions Tuesday at the 66th Annual Meeting and Exposition of the American Society of Hematology in San Diego. This is a special honor, given that only the top six late-breaking abstracts are selected for presentation each year.

“This is the first study to show how genetic traits related to living at high altitudes can affect disease and treatment outcomes,” said Song, assistant professor in the Division of Hematology & Hematologic Malignancies. “Our findings suggest that this NFKB1 gene variant could help predict inflammation levels and treatment success.”

Prchal and Song’s research is drawn from a years-long genomic study of the Aymara, an indigenous population living in the Andes Mountains of South America. About 2.3 million Aymara live in northwest Argentina, Bolivia, Chile and Peru.

NFKB1, in many cases, is a gene that activates inflammation. Chronic inflammation can lead to abnormal cell growth and cancer. 

Around 90% of the Aymara people have an enriched variant of the gene, according to Song and her team, though it is not unique to their population. It is also present in roughly 30% of Europeans, Hispanics and Asians.

Song and Prchal recognized that with blood cancers, characterized by increased inflammation, those with the enriched variant of the NFKB1 gene had lower inflammation and better responses to treatment.

This effect of the gene variant could stem from a protective evolutionary measure against blood clots and other inflammatory responses at high altitude.

“The molecular pathway happened to be discovered through research unrelated to cancer but instead by looking at evolutionary accommodation to high altitude,” Prchal said. “But when we found that this pathway changes inflammation, and that it also happens to be in people who aren’t Aymara, we could quickly use this knowledge to analyze cells we had from our patients.”

Prchal, who holds the Charles A. Nugent, MD, and Margaret Nugent Endowed Professorship in Medicine/Hematology, is a renowned expert in the treatment of polycythemia vera, essential thrombocythemia, and other myeloproliferative neoplasms— types of blood cancer that cause the bone marrow to produce too many red blood cells, white blood cells, and platelets, and increase the risk of blood clots. These diseases may escalate into more severe blood diseases, such as myelofibrosis and leukemia.

“What we found is that 30% of patients with polycythemia vera and essential thrombocythemia are actually better off with the Andean gene variant of NFKB1 than people without,” Song and Prchal said. “They are all more likely to get complete remission with treatment and may have a better course.”

They hope that the identification of the enriched variant of the NFKB1 gene could lead to drug therapies for myeloproliferative neoplasms that will replicate the variant’s capabilities.

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The Huntsman Cancer Institute research described in this release is supported by the National Institutes of Health/National Cancer Institute including P30 CA042014, MPN foundation challenge grant, Brown Foundation, and Huntsman Cancer Foundation.  

• Heather Simonsen Huntsman Cancer Institute public relations
  801-581-3194 public.affairs@hci.utah.edu