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Publications

Joint profiling of proteins and DNA in single cells reveals extensive proteogenomic decoupling in leukemia


Demaree, Benjamin, Delley, Cyrille L., Vasudevan, Harish N., Peretz, Cheryl A. C., Ruff, David, Smith, Catherine C., Abate, Adam R.
Nature Communications Nov 2021
Abstract

Studies of acute myeloid leukemia rely on DNA sequencing and immunophenotyping by flow cytometry as primary tools for disease characterization. However, leukemia tumor heterogeneity complicates integration of DNA variants and immunophenotypes from separate measurements. Here we introduce DAb-seq, a technology for simultaneous capture of DNA genotype and cell surface phenotype from single cells at high throughput, enabling direct profiling of proteogenomic states in tens of thousands of cells. To demonstrate the approach, we analyze the disease of three patients with leukemia over multiple treatment timepoints and disease recurrences. We observe complex genotype-phenotype dynamics that illustrate the subtlety of the disease process and the degree of incongruity between blast cell genotype and phenotype in different clinical scenarios. Our results highlight the importance of combined single-cell DNA and protein measurements to fully characterize the heterogeneity of leukemia.

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Area

Heme

Institution Type

Academia

Indication / Modality

Acute Myleoid Leukemia (AML)

Goal of Study

MRD, Therapeutic Resistance, Longitudinal, Disease Progression

Key Genes

FLT3, KRAS

PAD Project

No

Analytes Assessed

SNV, InDels, Extracellular Protein

Sample Storage

Fresh Frozen

Sample Prep

Whole Cells

Sample Type

Patient Material

Tissue / Organ

Bone Marrow Aspirates

Species

Human

Panel Used

Catalog AML Panel

Proof Point Demonstrated

Multi-omics, Clonality
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