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

Troy T. Robinson et al.

Measurable residual disease (MRD), defined as the population of cancer cells which persists following therapy, serves as the critical reservoir for disease relapse in acute myeloid leukemia (AML) 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. Herein, we developed a single cell (sc) MRD assay by combining flow cytometric enrichment of the targeted precursor/blast population with integrated scDNA 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/pre-leukemic and leukemic cells surviving AML therapy.


Troy T. Robinson


The genomic landscape of pediatric acute lymphoblastic leukemia
Samuel W. Brady
Nature Genetics
Detection of early seeding of Richter transformation in chronic lymphocytic leukemia
Ferran Nadeu
Nature Medicine (2022)
Modeling clonal evolution and oncogenic dependency in vivo in the context of hematopoietic transformation
Bowman RL
BioRxiv (2022)
Distinct patterns of clonal evolution drive myelodysplastic syndrome progression to secondary acute myeloid leukemia
Guess T
Blood Cancer Discovery (2022)