A prospective study from a Canadian tertiary care center has evaluated optical genome mapping (OGM) as a first-line test in the diagnostic workup of adult acute leukemia, reporting its performance alongside karyotyping, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS).
Current cytogenetic workflows rely on a combination of these methods, each with limitations. Karyotyping may miss cryptic or complex abnormalities, FISH is restricted to targeted regions, and NGS panels are less effective at detecting large structural variants. OGM offers genome-wide structural variant detection by imaging labeled ultra–high-molecular-weight DNA molecules, enabling identification of both large and smaller genomic alterations.
In analytical validation using 83 samples, OGM showed 100 percent specificity, 96 percent sensitivity, and 98 percent accuracy, with a limit of detection of approximately 10 percent variant allele fraction. Results were reproducible across runs and operators.
Following implementation in November 2023, 200 consecutive adult acute leukemia cases were analyzed, including acute myeloid leukemia, B-cell and T-cell acute lymphoblastic leukemia, and related high-grade neoplasms.
OGM identified 640 reportable variants compared with 444 detected by karyotype and FISH. Variants were stratified by clinical significance, with 25 percent classified as tier 1A.
Using karyotype and FISH as reference methods, OGM demonstrated 100 percent specificity, 95.6 percent sensitivity, and 97.3 percent accuracy in the clinical cohort. Missed findings were mainly low-level aneuploidies and did not affect diagnosis.
OGM provided additional clinically relevant findings beyond standard testing in 109 cases. In 35 cases, these findings led to changes in diagnostic classification and/or risk stratification. These included variants not detected by karyotype or FISH, three KMT2A partial tandem duplications missed by NGS, and clinically relevant abnormalities in cases where karyotyping failed.
The added diagnostic yield was most evident in B-cell acute lymphoblastic leukemia and mixed phenotype acute leukemia, where OGM more frequently identified alterations affecting classification or risk.
Turnaround times for OGM were longer than for karyotyping, with preliminary reports at approximately 9 days and final reports at 13 days. As a result, OGM was used in parallel with conventional cytogenetics rather than as a replacement.
These findings indicate that OGM can increase detection of clinically relevant genomic alterations in acute leukemia and may support diagnostic classification and risk assessment when integrated into existing laboratory workflows.
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