Background Cytogenetic analysis encompasses a suite of standard-of-care diagnostic testing methods that is routinely applied in cases of acute myeloid leukemia (AML) to assess chromosomal changes that are clinically relevant for risk classification and treatment decisions.

Objective 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.

Methods Archival patient 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.

Results GPM showed 100% concordance for all specific variants that have associated impacts on risk stratification as defined by ELN 2022 criteria, and a 72% concordance rate when considering all variants reported by the FH cytogenetic lab. GPM identified 39 additional variants, including variants of known clinical impact, not observed by cytogenetics.

Conclusions GPM is an effective solution for the evaluation of known AML-associated risk variants and a source for biomarker discovery.

SME, MM, and IL are employees of Phase Genomics, Inc. the developers of the technology described in this publication.

This work was supported by an SBIR Phase II grant from NCI/NIH R44CA278140 to SME and Phase Genomics. This work is also partially supported by UG1 CA233338-02, and CA175008-06 to JR at FHCC.

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Data will be made publicly available through dbGAP upon acceptance at a peer-reviewed journal.