Pb1845: a Multiomic, Single-cell Measurable Residual Disease (scmrd) Assay for Phasing Dna Mutations and Surface Immunophenotypes
Year: 2023
Type: conference-abstract
Abstract: Topic: 4. Acute myeloid leukemia - Clinical Background: The small population of cancerous cells that remain following treatment, known as measurable residual disease (MRD), is a strong predictor of relapse in acute myeloid leukemia (AML). Often, these refractory cells have gained additional resistance mutations or changed their surface immunophenotypes in ways that preclude detection or discrimination from preleukemic clones by current gold standard flow cytometry or bulk NGS assays. For this reason, a multi-omic single cell MRD assay could offer a more comprehensive indicator of relapse and the potential for faster response. Aims: Here, we present a new single-cell MRD (scMRD) assay with a 0.01% limit of detection, while also giving single cell clonal architecture and immunophenotyping to not only identify residual leukemia cells, but also identify putative DNA or protein targets for salvage therapy. Methods: The assay enables rare-cell detection on a standard Mission Bio Tapestri run by adding: (i) an upfront bead-based protocol to enrich for blast cells, (ii) a DNA and protein panel specifically designed for AML MRD diagnosis and treatment in alignment with both ICC and ELN guidelines, and (iii) a new automated analysis pipeline to evaluate single cell multiomics output. In addition, the multiplexing of up to three patient samples combined in one run via germline identification further reduces per sample costs and increases throughput. Results: Through the use of Mission Bio’s technology for detecting DNA variants in single-cells, this pipeline leverages variant-specific error modeling and single-cell co-occurrence to sensitively detect de novo variants, reducing false positive rates to achieve an LOD that meets and exceeds the recommended 0.1% cutoff for MRD-positivity by flow cytometry. It furthermore reconstructs the phylogenetic tree of the detected MRD cells, presents their surface protein signature and arm-level copy number changes. To demonstrate these features on MRD down to 0.01%, we present data from samples constructed by titrating diseased cells into healthy bone marrow cells before processing them with the scMRD assay. Summary/Conclusion: Combining high sensitivity with multi-omics, this assay offers a potential scalable solution for comprehensive AML MRD detection and guiding therapeutic decision-making.Keywords: Acute myeloid leukemia, Measurable residual disease, Immunophenotype, Somatic mutation
Source: HemaSphere
Authors: Charlie Murphy, Kathryn Thompson, Lubna Nousheen, Aaron Llanso, Todd Druley, Adam Sciambi
Institution: Mission Bio (United States)
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W4386102437