Can Optical Genome Mapping Replace Bone Marrow Biopsies in Acute Myeloid Leukemia?
Authors: Hahn Logan , DeCoteau John , Mochoruk Karen , Tanumihardja Gabriela , Giasson Holly , Geyer Ronald , Sabry Waleed , Elemary Mohamed , Stakiw Julie , MacKay Rebecca Ellyn , Bosch Mark 
Published: December 2024

Background
Identifying structural variants (SVs) is essential for targeted treatment and prognosis in acute myeloid leukemia (AML) patients. Current cytogenetic techniques like karyotyping and fluorescence in situ hybridization (FISH) face challenges, leading to test failure rates of over 20% (Pullarkat 2008; Grimwade 1998). Additionally, conventional cytogenetic analysis yields normal or non-specific profiles for over one third of AML patients with analyzable karyotypes (Mawad 2012). Optical genome mapping (OGM) poses a potential solution to these limitations. OGM involves the identification of SVs through analysis of ultra-high molecular weight DNA and does not require dividing cells for analysis. OGM has much higher sensitivity than karyotyping and is typically at the 5% variant allele fraction level. Given the resolution of this technique, we hypothesize that OGM results from peripheral blood (PB) and bone marrow (BM) specimens are highly concordant, thereby obviating the need for diagnostic BM biopsies in many AML patients. In the present study, we determine the concordance rate of results obtained through OGM on PB, OGM on BM and conventional cytogenetics in a small cohort of patients with AML.
Methods
Fourteen consecutive adult patients with AML and greater than 20% blasts in PB, BM, or both were included in the analysis. Conventional cytogenetics (karyotype and FISH) and OGM were performed on BM or PB samples. Twelve patients had OGM performed on both PB and BM specimens. Additionally, 14 BM and 8 PB samples were analyzed by next generation sequencing (NGS) using the Oncomine Myeloid Research Assay from ThermoFisher, which includes a 40-gene DNA panel and an RNA panel covering 29 fusion drivers, in order to compare findings based on European LeukemiaNet (ELN) 2022 risk categories.
Results
The mean age at diagnosis was 62 years (range: 20-79) The sample consisted of 8 women and 6 men. The mean percentage of PB blasts at diagnosis was 28% (range: 0.1-88), whereas the mean percentage of BM blasts was 55% (range: 20-88%). Two patients had less than 5% blasts in the PB. By using conventional cytogenetics, 11 patients were categorized as having intermediate risk, while 3 were in the adverse risk category. When comparing conventional cytogenetics and OGM performed on either BM or PB specimens, there was agreement in all 14 cases in terms of ELN risk category. In the patients (n=12) who had OGM performed on both their PB and BM samples, there were no discrepancies detected. In the 8 patients who had OGM and NGS performed on both PB and BM, there was also complete agreement in terms of ELN risk stratification.
Conclusions
In this ongoing study, OGM completed on BM or PB demonstrated all the same SVs detected by conventional cytogenetics. Additionally, there was total agreement between OGM results obtained on PB or BM, even in patients with low levels of circulating blasts. These results indicate that utilizing OGM could enable clinicians to perform necessary testing for AML patients through a more sensitive and less invasive method, potentially enhancing outcomes.