Case Reviews in Acute Myeloid Leukemia

Traditional standard-of-care testing in acute myeloid leukemia (AML) often yields incomplete genomic profiles, potentially missing alterations critical for accurate risk stratification and treatment decisions. In this Grand Rounds webinar recording, Laura Dillon, PhD, FACMG of Virginia Tech led an expert, case-based review demonstrating how whole-genome sequencing (WGS) uncovers alterations frequently missed by conventional cytogenetic and molecular methodologies.

The session focused on the MEASURE Genome Atlas, a prospective multi-center study of patients with AML. Laura presented a focused review of the study’s validation of WGS for the genomic characterization of AML, comparing its performance with clinical standard-of-care testing across variant classes, including structural variants, copy-number changes, and low-allele-fraction alterations. In-depth discussion also included four real-world cases from the study, including patients who had modifications to their risk stratification by ELN 2022 guidelines following WGS findings. Case reviews included a cryptic KMT2A::UBASH3B fusion, a splice-disrupting STAG2 deletion missed by targeted panel sequencing, a cytogenetically cryptic NUP98::KDM5A translocation, and a low-allele-fraction KMT2A partial tandem duplication undetected by copy-number–based methods.

Through guided discussion, participants gained insight into how comprehensive genome-wide analysis can refine AML risk stratification, inform targeted therapy considerations, and address limitations of existing workflows for complex cases.

Explore more case reviews from our Grand Rounds in Genomics Medicine sessions here.

Speaker

Laura Dillon, PhD, FACMG
Research Associate Professor
Virginia Tech FBRI Cancer Research Center