Updated genomic landscape for pediatric acute myeloid leukemia enables new treatment possibilities

AML classification provides biological insight and potential clinical guidance

The reasons why different features give rise to AML in children and adults have yet to be fully understood. The normal accumulation of mutations during aging may explain many adult AML cases. In contrast, fusion oncoproteins, aberrant proteins resulting in the fusion of two separate genes, are major drivers for many pAML cases and were shown to account for over 70% of cases in this new study. Although each molecular category has a unique driver, some show very similar transcriptional and mutational profiles, which stood out to the researchers. “Some categories show very similar transcriptional profiles, indicating that the background biology is similar and can be potentially treated by similar drugs,” said Umeda.

This work offers a clear path forward for clinicians to identify distinct pAML sub-types and for larger collaborative groups to define cancer more accurately. “The World Health Organization [WHO] issued new classifications for hematological cancers in 2022, mostly based on adults,” Klco explained. “We recognized that many of the recurrent alterations we found in pAML aren’t even mentioned. Some of these sub-types have a significant impact on outcomes.” 

Correct classification will allow clinicians worldwide to understand their pAML patients better and offer guidance to treat cases as low-risk or high-risk. In fact, through their analysis, they determined a strong association between the new sub-types and clinical outcomes. “The study definitely fills a lot of gaps in the current classification of pAML,” Ma confirmed. “It provides a risk stratification strategy that we hope will provide clinicians with a simpler road to accurate diagnosis and optimal treatment in the future.”

Authors and funding

The study’s other authors include Tamara Westover, Yonghui Ni, Guangchun Song, Jamie Maciaszek, Michael Rusch, Delaram Rahbarinia, Scott Foy, Michael Walsh, Priydarshini Kumar, Yanling Liu, Yiping Fan, Gang Wu, Xiaotu Ma, Lu Wang, Jeffrey Rubnitz, and Stanley Pounds of St. Jude; Benjamin Huang of the University of California San Francisco, Sharyn Baker of the Comprehensive Cancer Center, The Ohio State University, and Todd Alonzo of Keck School of Medicine, University of Southern California.

The study was supported by grants from The National Institutes of Health (P30 CA021765, Cancer Center Support Grant and Developmental Fund Award and U54 CA243124), the Fund for Innovation in Cancer Informatics, the Burroughs Wellcome Fund, the V Foundation, and ALSAC, the fundraising and awareness organization of St. Jude.