Evaluation of acute myeloid leukemia using genomic proximity mapping-based next generation cytogenomics

Cytogenetic analysis encompasses a suite of standard-of-care diagnostic testing methods that is applied routinely in cases of acute myeloid leukemia (AML) to assess chromosomal changes that are clinically relevant for risk classification and treatment decisions. In this study, we assess the use of Genomic Proximity Mapping® (GPM) for cytogenomic analysis of AML diagnostic specimens for detection of cytogenetic risk variants included in the European Leukemia Network (ELN) risk stratification guidelines. Archival patients' samples (N=48) from the Fred Hutchinson Cancer Center Leukemia Bank with historical clinical cytogenetic data were processed for GPM and analyzed with the CytoTerra cloud-based analysis platform. GPM showed 100% concordance for all specific variants that have associated impacts on risk stratification as defined by ELN 2022 criteria and 78% concordance when considering all variants reported by the Cytogenetics Laboratory at Fred Hutchinson Cancer Center. Notably, the percentage of blasts (ranging from 5-96%) did not have a clear effect on the ability to detect these variants. In two cases, GPM identified a recurrent inv(9)(p13.3p13.1). These findings demonstrate GPM's effectiveness for the evaluation of known AML-associated risk variants and a source for biomarker discovery.