Optical genome mapping detects cryptic high-risk and targetable abnormalities in adult AML

Area of Science:

• Genomics
• Hematology
• Cancer Research

Background:

• Acute myeloid leukaemia (AML) risk stratification is crucial for treatment decisions, relying on European LeukemiaNet (ELN) 2022 guidelines.
• Conventional cytogenetic methods like chromosomal banding analysis (CBA) and fluorescence in situ hybridization have limitations in detecting subtle or 'cryptic' genetic events.

Purpose of the Study:

• To evaluate the diagnostic utility of Optical Genome Mapping (OGM) in identifying additional cytogenetic abnormalities in AML patients.
• To assess the impact of OGM findings on the ELN 2022 risk classification and explore potential therapeutic targets.

Main Methods:

• Retrospective analysis of 100 adult AML patients with low-complexity cytogenetic abnormalities.
• Application of Optical Genome Mapping (OGM) alongside conventional cytogenetics (CBA).
• Comparison of OGM-detected abnormalities with CBA findings and assessment of impact on ELN 2022 risk stratification.

Main Results:

• OGM detected 91.4% of abnormalities found by CBA and provided additional information in 37% of patients.
• Fourteen percent of patients were reclassified to an unfavorable cytogenetic group, and 7.7% to the ELN 2022 adverse risk group.
• Cryptic KMT2A and NUP98 lesions, potential therapeutic targets, were identified in 10% of cases.

Conclusions:

• OGM offers significant incremental diagnostic value in low-complexity AML by detecting high-risk and targetable cryptic abnormalities.
• OGM serves as a valuable complementary tool to conventional cytogenetics for refining AML risk stratification.
• Findings suggest a trend towards poorer outcomes in patients reclassified to adverse risk groups by OGM, warranting further investigation.