78. Next generation cytogenomics improves patient risk stratification in acute myeloid leukemia

Abstract

The European Leukemia Network (ELN) has established criteria for patient risk stratification based on cytogenetic abnormalities in observed in acute myeloid leukemia (AML). Risk stratification based on cytogenetic analysis is commonly used to guide therapy selection and overall patient care. Proximity ligation sequencing (PLS) is a next generation cytogenomic method that uses short-read NGS to capture ultra-long-range genomic contiguity and detect chromosome abnormalities including those in the ELN risk stratification. To test the utility of PLS in evaluating cytogenetic risk in AML, we performed a retrospective study of AML cases gathered from clinical archives. In all, libraries from 95 samples were prepared using the OncoTerra PLS library preparation kit and sequenced on one of three platforms: Illumina, Element, or Singular short-read sequencing platforms. Libraries sequenced across all three platforms passed QC metrics for library performance. Patient risk based on variants identified by the OncoTerra PLS analytic platform and the reported standard-of-care cytogenetics were assessed following the ELN 2022 guidelines. The predictive power of OncoTerra and standard-of-care cytogenetics were evaluated based on the overall survival of patients segregated into favorable, intermediate, and adverse risk categories. Statistical comparison of Kaplan-Meier analysis between OncoTerra and standard-of-care cytogenetics demonstrated that PLS significantly improved the segregation of patient outcomes across risk groups. These findings show that PLS has the potential significantly improve cytogenetic risk stratification within the context of established ELN risk variants for AML using short-read sequencing platforms.