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Publications

Single-cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia


Troy M. Robinson, Robert L. Bowman, Sonali Persaud, Ying Liu, Rosemary Neigenfind, Qi Gao, Jingping Zhang, Xiaotian Sun, Linde A. Miles, Sheng F. Cai, Adam Sciambi, Aaron Llanso, Christopher Famulare, Aaron Goldberg, Ahmet Dogan, Mikhail Roshal, Ross L. Levine, Wenbin Xiao
Science Advances Sep 2023
Abstract

Measurable residual disease (MRD), defined as the population of cancer cells that persist following therapy, serves as the critical reservoir for disease relapse in acute myeloid leukemia and other malignancies. Understanding the biology enabling MRD clones to resist therapy is necessary to guide the development of more effective curative treatments. Discriminating between residual leukemic clones, preleukemic clones, and normal precursors remains a challenge with current MRD tools. Here, we developed a single-cell MRD (scMRD) assay by combining flow cytometric enrichment of the targeted precursor/blast population with integrated single-cell DNA sequencing and immunophenotyping. Our scMRD assay shows high sensitivity of approximately 0.01%, deconvolutes clonal architecture, and provides clone-specific immunophenotypic data. In summary, our scMRD assay enhances MRD detection and simultaneously illuminates the clonal architecture of clonal hematopoiesis/preleukemic and leukemic cells surviving acute myeloid leukemia therapy.

VIEW

Area

Heme

Institution Type

Academia

Indication / Modality

Acute Myleoid Leukemia, Acute Myleoid Leukemia (AML)

Goal of Study

MRD

Key Genes

DNMT3A, TP53, NRAS, IDH2, FLT3, JAK2, RUNX1, SF3B1, SRSF2, SETBP1, TET2, NPM1, U2AF1, CBL, STAG2, KRAS, PTPN11, WT1, ASXL1

PAD Project

No

Analytes Assessed

SNV, InDels, Extracellular Protein

Sample Storage

Fresh Frozen

Sample Prep

Whole Cells

Sample Type

Patient Material, PBMC

Tissue / Organ

Bone Marrow Aspirates

Species

Human

Panel Used

Custom

Proof Point Demonstrated

Better than Bulk, Cell Identity, Co-occurrence, Multi-omics, Sensitivity, Zygosity
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