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- Title
A single-cell survey of cellular hierarchy in acute myeloid leukemia.
- Authors
Wu, Junqing; Xiao, Yanyu; Sun, Jie; Sun, Huiyu; Chen, Haide; Zhu, Yuanyuan; Fu, Huarui; Yu, Chengxuan; E., Weigao; Lai, Shujing; Ma, Lifeng; Li, Jiaqi; Fei, Lijiang; Jiang, Mengmeng; Wang, Jingjing; Ye, Fang; Wang, Renying; Zhou, Ziming; Zhang, Guodong; Zhang, Tingyue
- 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.
- Subjects
ACUTE myeloid leukemia; HEMATOLOGIC malignancies; RIBOSOMAL proteins; PROGENITOR cells; HIERARCHIES
- Publication
Journal of Hematology & Oncology, 2020, Vol 13, Issue 1, pN.PAG
- ISSN
1756-8722
- Publication type
Article
- DOI
10.1186/s13045-020-00941-y