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 session, Laura Dillon, PhD, FACMG of Virginia Tech will lead an expert, case-based review demonstrating how whole-genome sequencing (WGS) uncovers alterations frequently missed by conventional cytogenetic and molecular methodologies. 

The session will focus on the MEASURE Genome Atlas, a prospective multi-center study of patients with AML. Laura will present 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 will also include three real-world cases from the study, including patients which had modifications to their risk stratification by ELN 2022 guidelines following WGS findings. Case reviews will include 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 will gain 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.