Single-cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia Journal Article
| Authors: | Robinson, T. M.; Bowman, R. L.; Persaud, S.; Liu, Y.; Neigenfind, R.; Gao, Q.; Zhang, J.; Sun, X.; Miles, L. A.; Cai, S. F.; Sciambi, A.; Llanso, A.; Famulare, C.; Goldberg, A.; Dogan, A.; Roshal, M.; Levine, R. L.; Xiao, W. |
| Article Title: | Single-cell genotypic and phenotypic analysis of measurable residual disease in acute myeloid leukemia |
| 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. |
| Keywords: | genetics; leukemia, myeloid, acute; flow cytometry; genotype; bioassay; immunophenotyping; biological assay; acute myeloid leukemia; humans; human |
| Journal Title: | Science Advances |
| Volume: | 9 |
| Issue: | 38 |
| ISSN: | 2375-2548 |
| Publisher: | Amer Assoc Advancement Science |
| Date Published: | 2023-09-22 |
| Start Page: | eadg0488 |
| Language: | English |
| DOI: | 10.1126/sciadv.adg0488 |
| PUBMED: | 37729414 |
| PROVIDER: | scopus |
| PMCID: | PMC10881057 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding authors are Wenbin Xiao and Ross Levine -- Source: Scopus |
