Integrated sequencing approach provides gold standard pediatric AML diagnosis

Acute myeloid leukemia (AML) has the highest mortality rate among all forms of childhood leukemia. This is in part due to its broad genetic diversity, including rare subtypes, which current clinical diagnostic practices struggle to identify accurately. Identifying the genes responsible for a patient’s cancer is vital for quickly designing treatment plans tailored for that patient. For Lu Wang, MD, PhD, St. Jude Department of Pathology, current methods often fell short in detecting rare AML subtypes, leaving a blind spot during diagnosis. 

“Cytogenetics is genome-wide, but low resolution, and targeted sequencing sometimes misses important information,” Wang said. “The next advancement must be integrated whole genome and whole transcriptome sequencing, and St. Jude has been providing this as a diagnostic testing method for years.”

The infrastructure already in place at St. Jude allowed the team to explore several combinations of sequencing techniques for accurate AML genetic evaluation. They highlighted their findings recently in Leukemia.

Sequencing combination leaves no stone unturned

The team used real-time data generated by different methodologies through diagnostic assessments of 153 patients. They found that combining the broad molecular profile range of whole genome sequencing (which looks at the entire genome) with advances in whole transcriptome sequencing (which looks just at expressed genes), they could be more confident in determining genetic drivers and molecular subtypes of leukemia. 

“The integrated approach allows us to make determinations with much more confidence, especially for novel findings,” said co-corresponding author Jeffery Klco, MD, PhD, Department of Pathology. “It provides important cross-validation, allowing us to issue the most robust and rigorous clinical reports.”

While this study focuses on AML diagnostic practices, the approaches can also be applied to other forms of leukemia and pediatric solid tumors. As access to these technologies improves nationally and worldwide, the guidelines provided by this study demonstrate the techniques’ value, while providing hospitals with a blueprint for their use. 

“Now is the right time to share our clinical experience; we’ve optimized the workflow, and sequencing costs and data processing pipelines have improved, making it easier for others to adopt,” Wang said. “More and more institutions are now realizing this is the future.”