European LeukemiaNet (ELN) guidelines recommend measurable residual disease (MRD) testing as standard of care after intensive induction therapy in acute myeloid leukemia (AML), with molecular methods preferred when the leukemia carries a trackable genomic marker. Current laboratory workflows focus almost entirely on DNA-level variants: mutations in NPM1, internal tandem duplications in FLT3, and hotspot single-nucleotide variants (SNVs) across AML-associated genes. That architecture serves roughly three-quarters of cases well, but the remaining 20 to 25 percent carry chromosomal fusion events that generate distinct RNA transcripts, and DNA-focused panels provide incomplete residual disease coverage for this group.
OGT announced the launch of the SureSeq myPanel Myeloid Fusion MRD Panel, an RNA-based next-generation sequencing (NGS) panel developed with Roswell Park Comprehensive Cancer Center and the first product OGT describes as dedicated to fusion event detection at MRD-level sensitivity in AML. In initial clinical research samples at Roswell Park, the fusion panel detected BCR::ABL1 and PML::RARA transcripts at serial dilutions as low as one percent tumor cells. It also measures MECOM (the gene encoding both MDS1 and EVI1) expression levels, a target whose overexpression carries adverse prognosis and less than 10 percent five-year overall survival in MECOM-rearranged AML.
Why do AML fusion transcripts resist DNA-based MRD detection?
Chromosomal translocations drive fusion-positive AML by producing chimeric messenger RNA (mRNA) transcripts, not a DNA mutation standard capture sequencing can detect. That distinction explains why DNA-based NGS MRD panels leave a monitoring gap for this patient subgroup: tracking fusion transcripts requires RNA-based methods, typically reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), rather than the DNA hybridization capture chemistry most contemporary NGS MRD assays use.
RT-qPCR has been the gold standard for fusion MRD monitoring for two decades. ELN guidelines recommend it for core-binding factor (CBF) AML, covering the RUNX1::RUNX1T1 and CBFB::MYH11 subgroups, and for acute promyelocytic leukemia (APL) monitored via PML::RARA, with sensitivity reaching 10⁻⁴ to 10⁻⁶. The method's core limitation is that it is single-target: each fusion transcript needs its own validated assay, so a laboratory monitoring multiple fusions must run separate workflows on separate instruments and reconcile results across systems.
Panel design: 20 fusion gene targets and MECOM expression in one assay
The SureSeq myPanel Myeloid Fusion MRD Panel targets 20 baited genes plus three housekeeping genes for expression normalization, covering AML-associated fusion partners across all 20 gene regions. It works as a standalone panel or alongside OGT's DNA-based SureSeq Myeloid MRD Plus NGS Panel, which covers 53 hotspot exons across 16 AML-associated genes, extending characterization to SNVs, indels, and FLT3 internal tandem duplications (ITDs). OGT-reported capabilities include:
- Fusion sensitivity: detection at one percent tumor cell sensitivity in serial dilutions, demonstrated for BCR::ABL1 and PML::RARA in initial Roswell Park clinical research samples
- MECOM quantification: measurement of expression levels to track 3q26-rearrangement-associated overexpression, a marker of adverse prognosis in AML
- Longitudinal tracking: integration with OGT's Interpret bioinformatics platform for visualization of fusion events and MECOM expression trends across multiple patient timepoints
- Combined MRD coverage: paired deployment with the SureSeq Myeloid MRD Plus NGS Panel to detect SNVs, indels, ITDs, and fusion transcripts within a shared NGS workflow
Sean Glenn, Vice Chair of Molecular Pathology and Director of the Advanced Molecular Diagnostics Laboratory at Roswell Park Comprehensive Cancer Center, put the panel's clinical research value in straightforward terms. "The addition of RNA fusion detection represents an important opportunity to broaden the reach of molecular MRD assessment to the approximately 20–25% of AML cases associated with fusion-driven disease," Glenn said. "By providing molecular markers of residual leukaemia that can be monitored over time, fusion transcripts can support residual disease assessment, including in samples that lack an informative DNA mutation."
RNA NGS, RT-qPCR, and flow cytometry fill different AML MRD roles
Each AML MRD method differs in analyte type, multiplexing capacity, and the share of cases it can address; the table below maps these attributes across the approaches a laboratory would typically evaluate.
| Testing approach | Analyte type | Primary targets | Variant coverage | Sensitivity |
|---|---|---|---|---|
| SureSeq myPanel Myeloid Fusion MRD Panel (OGT) | RNA | Fusion transcripts, MECOM expression | 20 baited gene regions covering AML-associated fusions including BCR::ABL1, PML::RARA | 1% tumor cells (BCR::ABL1, PML::RARA; initial clinical research study) |
| SureSeq Myeloid MRD Plus NGS Panel (OGT) | DNA | SNVs, indels, FLT3-ITDs | 53 hotspot exons from 16 AML-associated genes including FLT3 and NPM1 | As low as 0.01% variant allele frequency (VAF) |
| Standardized RT-qPCR (EAC/ELN-endorsed) | RNA | Single fusion transcripts per assay | CBF fusions, PML::RARA, BCR::ABL1, NPM1 | 10⁻⁴ to 10⁻⁶; one target per run |
| RNA-based NGS (research classification panels) | RNA | Broad discovery; not MRD-optimized | Variable; typically not validated for low-frequency residual disease | Varies; sensitivity at MRD levels not established for most |
| Multiparameter flow cytometry (MFC) | Protein (immunophenotype) | Leukemia-associated immunophenotype | Applicable to approximately 90% of AML; not fusion-specific | 10⁻³ to 10⁻⁴ |
The ELN's 2021 MRD recommendations and 2025 update favor RT-qPCR for molecular subtypes with standardized assays, while acknowledging that NGS-based MRD is increasingly relevant for patients whose disease falls outside those categories. For laboratories already running the Myeloid MRD Plus panel, the fusion panel runs on the same SureSeq workflow and Interpret software, reducing the operational barrier to adding RNA-based fusion tracking. Whether paired deployment delivers clinically actionable information beyond RT-qPCR for established fusion subtypes, or its primary value lies in less common and novel fusions, will emerge from prospective validation studies.
OGT CEO Adrian Smith addressed the fragmented, multi-assay workflows the panel is built to replace. "Important fusion signals are difficult to identify when workflows depend on multiple assays or have insufficient sensitivity," Smith said. "This panel has the potential to capture a wide range of disease-associated fusion events at MRD-levels of sensitivity that may otherwise be missed, and thus provides a broader genomic profile of AML samples for deeper insights."
RNA fusion NGS extends AML MRD monitoring where DNA panels stop
The SureSeq myPanel Myeloid Fusion MRD Panel addresses a structural blind spot in AML residual disease testing by bringing RNA-based fusion tracking into a standardized NGS workflow at one percent tumor cell sensitivity, covering the approximately 20 to 25 percent of cases that DNA mutation panels cannot monitor. The panel carries a research use only designation, and prospective validation in larger patient cohorts will establish how its performance in serial dilutions translates to post-treatment clinical samples and whether RNA-NGS MRD adds actionable information alongside established RT-qPCR methods for the most common fusion subtypes. For laboratories building end-to-end AML MRD workflows, paired deployment with the Myeloid MRD Plus NGS Panel offers a path to covering mutation-driven and fusion-driven disease from a single NGS platform.
This article is based on a press release issued by OGT and was produced under Drug Discovery News' AI Editorial Guidelines.
