Abstract 109P
Background
The small population of cancerous cells that remain following treatment, known as measurable residual disease (MRD), is the major cause of relapse in acute myeloid leukemia (AML). Usually, these refractory cells have gained additional resistance mutations or changed their surface immunophenotypes in ways that preclude detection and phasing by current gold standard flow cytometry or bulk NGS assays. For this reason, a multiomic single-cell MRD (scMRD) assay could offer a more comprehensive indicator of relapse and the potential for faster response.
Methods
Here, we present a new scMRD assay with a 0.01% limit of detection that provides single-cell clonal architecture and immunophenotyping to not only identify residual leukemia cells, but also identify putative DNA or protein targets for salvage therapy. 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, and (iii) a new, automated analysis pipeline to evaluate single-cell multiomics output. By utilizing Mission Bio’s single-molecule DNA sensitivity for single cells, this pipeline can identify and correlate co-occurring de novo variants, thereby reducing false positive rates. It furthermore can create phylogenetic trees of the detected MRD cells and present their surface protein signature and arm-level copy number. 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
To demonstrate these features, we applied the scMRD assay to banked bone marrow aspirate samples from 3 patients. The scMRD assay resolved the clonal architecture identifying multiple co-occurring mutations and readily distinguished pre-leukemic from leukemic clones. The integration of genotype and immunophenotypic further enhanced MRD detection by identifying genotype-specific protein expression patterns.
Conclusions
By combining high sensitivity with multiomics, this assay offers a potential scalable solution for comprehensive MRD detection that guides therapeutic decision-making.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Mission Bio.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
62P - Role of IL6 (C-174G) polymorphism in the development of cervical intraepithelial neoplasia
Presenter: Tatyana Abakumova
Session: Cocktail & Poster Display session
Resources:
Abstract
63P - The impact of disruption of melatonin secretion on the structural-functional changes of the microbiome and the role of the melatonin-microbiome axis in the initiation of carcinogenesis
Presenter: Alexandre Tavartkiladze
Session: Cocktail & Poster Display session
Resources:
Abstract
64P - Acidosis induces ferroptosis of breast cancer via ZFAND5/SLC3A2 axis with the synergistic effect of metformin and facilitates M1 macrophage polarization
Presenter: Hanchu Xiong
Session: Cocktail & Poster Display session
Resources:
Abstract
65P - Transmembrane distribution of phosphatidylethanolamine in plasma membrane of ovarian cancer cells under conditions mimicking tumor microenvironment
Presenter: Darya Savenkova
Session: Cocktail & Poster Display session
Resources:
Abstract
66P - Metabolic regulation of GMP- and MDP-derived macrophages in glioblastoma
Presenter: Liam Wilson
Session: Cocktail & Poster Display session
Resources:
Abstract
67P - Inflammation status and sarcopenia synergistically impact outcomes in cancer patients (pt) treated with ImmunOtherapy (IO) within the framework of a Molecular Pre-screening program (MP) and a spEcial Medication (ME) program
Presenter: Lucia Notario Rincon
Session: Cocktail & Poster Display session
Resources:
Abstract
68P - The role of systemic reprogramming of GMPs in improving outcomes in glioblastoma
Presenter: Aline Atallah
Session: Cocktail & Poster Display session
Resources:
Abstract
69P - Integrated OMIC analysis reveals arginine and proline metabolism plays critical role in hypoxia-induced oral squamous cell carcinoma
Presenter: Avinash Singh
Session: Cocktail & Poster Display session
Resources:
Abstract
70P - Individualising methotrexate dose based on MTHFR gene polymorphisms in acute lymphoblastic leukemia
Presenter: Meher Konatam
Session: Cocktail & Poster Display session
Resources:
Abstract
71P - Single nucleotide polymorphisms in the folate metabolic pathway genes and global DNA methylation in ovarian cancer
Presenter: Sandro Surmava
Session: Cocktail & Poster Display session
Resources:
Abstract