Can Optical Genome Mapping Replace Bone Marrow Biopsies in Acute Myeloid Leukemia?
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".