December 10, 2024
Author(s): Mary Caffrey
Questions about why an indigenous population living the Andes Mountains of South American had elevated hemoglobin led to the discovery that a variant linked to living at high altitude is also tied to reduced inflammation, as well as improved response to a therapy used to treat myeloproliferative neoplasms (MPNs).1
Jihyun Song, PhD | Image credit: University of Utah
The research to be presented today at the 66th American Society of Hematology Annual Meeting & Exposition in San Diego, California, could lead to more precise treatments for polycythemia Vera (PV) and essential thrombocythemia (ET). Today, these 2 are treated with ropeginterferon-α (Besremi), and the work led by Jihyun Song, PhD, of Huntsman Cancer Institute at the University of Utah, now shows that populations with Andean enriched NFKB1 haplotype respond better to ropeginterferon-α.
The study has been accepted for publication in Nature Communications.
PV and ET are both associated with overproduction of blood cells; PV causes the bone marrow to produce too many red blood cells, while ET produces too many platelets. Both PV and ET can lead to chronic inflammation, increase the risk of blood clots, and progress to leukemia. These conditions also increase hypoxia-inducible factors (HIFs), which can impact the survival of cancer cells in low-oxygen environments.
At a press briefing prior to Song’s presentation today, senior author Josef T. Prchal, MD, a physician scientist who holds the Charles A. Nugent, MD, and Margaret Nugent Endowed Professorship in Medicine/Hematology at the University of Utah, explained that the genetic variants that developed over time to allow the Aymara people survive in the Andes can be seen in some other populations—and they correlate with some differences in MPN phenotypes.
Josef Prchal, MD | Image credit: Photo supplied by ASH
“Our study suggests that with genotyping, the NFKB1 variant can be used as a biomarker for determining which patients may be more or less responsive to ropeginterferon-α treatment,” Prchal said.
He opened his remarks with an overview of how populations evolve with their environments; not only the Aymara but also Tibetans and Ethiopians have adapted to altitude in different ways, which he explored in earlier papers in Science2 and Nature Genetics,3 among others.
It is known that when humans spend time high altitude, their bodies adapt to reduced oxygen levels by increasing hemoglobin concentrations in the blood. This allows the body to carry more oxygen. Prchal explained how Song took this knowledge further. “We set up to try to find the gene which explains the hemoglobin,” he said.