Prospective evaluation of genome sequencing to compare conventional cytogenetics in acute myeloid leukemia

Acute myeloid leukemia (AML) can be classified into multiple genetic subtypes based on recurrent pathogenic structural variants (SVs), copy number abnormalities (CNAs), and single nucleotide variants (SNVs) that inform prognostication and clinical management [ 1 , 2 ]. Karyotype analysis is considered mandatory in the evaluation of AML. If karyotype analysis fails, fluorescence in situ hybridization (FISH) can be used as an alternative technique per ELN 2022 [ 2 ]. Recent reports have proposed whole genome sequencing (WGS) as an alternative methodology to karyotyping and FISH [ 3 , 4 ]. MPseq is one example of a WGS technique optimized for the detection of genome-wide SVs and CNAs [ 5 ]. However, previous studies have not directly assessed the prognostic utility of WGS approaches in identifying genetic abnormalities above gold-standard cytogenetic approaches within an unbiased, prospective setting.