UNC Lineberger Comprehensive Cancer Center researchers have demonstrated a faster, more cost-effective approach to analyzing the genetic makeup of pediatric acute leukemia. Determining a cancer’s genomic classification is critical to developing a more effective treatment plan tailored to a patient’s tumor.
Their findings were published in Leukemia.
UNC Lineberger’s Thomas Alexander, MD, MPH, assistant professor of pediatrics, and Jeremy Wang, PhD, associate professor of pathology and laboratory medicine and genetics, are the paper’s corresponding authors. Julie Geyer, PhD, a postdoctoral research assistant in the Wang lab, is the first author.
The study enrolled 57 pediatric patients diagnosed with either B-cell acute lymphoblastic leukemia (B-ALL) or acute myeloid leukemia (AML). Using nanopore DNA sequencing technology, the researchers identified the specific genetic alterations in all cases within 48 hours — and in some cases, within 15 minutes. This breakthrough could significantly speed up diagnosis, reduce costs and help doctors start targeted treatments more quickly, improving care for children with leukemia.
“Genomic classification of leukemia is not available for most patients in the world due to a lack of trained workforce and insufficient resources. Even in high-income countries, the process is labor-intensive, expensive and often incomplete,” Alexander said. “Our driving motivation is to develop a diagnostic test that is accessible to most of the world to close the diagnostic testing gap.”
The researchers demonstrated they can identify clinical genomic information for children with acute leukemia using adaptive sampling, a technique that uses nanopore sequencing to target specific genetic regions. This approach is more flexible, scalable and cost-effective than current methods for determining a cancer’s genomic classification.
“Adaptive sampling can be easily adjusted and updated with new targets or for different purposes without relying on new supply chains or wet lab validation,” Wang said. “On the same assay without additional wet lab work or sequencing, we also demonstrated the potential for identifying pharmacogenomic variants, with implications for treatment.”
Alexander and Wang said this simpler, less expensive, more comprehensive approach has significant implications in low-resource settings where clinical genomic classification is unavailable or incomplete. In high-income countries, it has the potential to simplify molecular pathology for acute leukemia, improve turnaround time and provide more comprehensive clinical findings.
Authors and disclosures
A complete listing of authors and disclosures is available in the published paper.
This work was supported by the National Institutes of Health (R21CA259926 and R01CA293366) and the University Cancer Research Fund.