A single-cell survey of cellular hierarchy in acute myeloid leukemia
- PMID: 32977829
- PMCID: PMC7517826
- DOI: 10.1186/s13045-020-00941-y
A single-cell survey of cellular hierarchy in acute myeloid leukemia
Abstract
Background: Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes.
Methods: Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells.
Results: From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic "cancer attractor" that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape.
Conclusions: We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.
Keywords: Acute myeloid leukemia; Cancer attractor; Microwell-seq; Ribosomal protein; Single-cell mRNA sequencing; Single-molecule real-time sequencing.
Conflict of interest statement
The authors declare no competing financial interest.
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References
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- Timilshina N, Breunis H, Tomlinson GA, Brandwein JM, Buckstein R, Durbano S, et al. Long-term recovery of quality of life and physical function over three years in adult survivors of acute myeloid leukemia after intensive chemotherapy. Leukemia. 2019;33(1):15–25. doi: 10.1038/s41375-018-0162-5. - DOI - PubMed
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