A single-cell survey of cellular hierarchy in acute myeloid leukemia

• Main Authors: Junqing Wu, Yanyu Xiao, Jie Sun, Huiyu Sun, Haide Chen, Yuanyuan Zhu, Huarui Fu, Chengxuan Yu, Weigao E., Shujing Lai, Lifeng Ma, Jiaqi Li, Lijiang Fei, Mengmeng Jiang, Jingjing Wang, Fang Ye, Renying Wang, Ziming Zhou, Guodong Zhang, Tingyue Zhang, Qiong Ding, Zou Wang, Sheng Hao, Lizhen Liu, Weiyan Zheng, Jingsong He, Weijia Huang, Yungui Wang, Jin Xie, Tiefeng Li, Tao Cheng, Xiaoping Han, He Huang, Guoji Guo
• Format: Article
• Language: English
• Published: BMC 2020-09-01
• Series: Journal of Hematology & Oncology
• Subjects: Acute myeloid leukemia; Single-cell mRNA sequencing; Microwell-seq; Ribosomal protein; Single-molecule real-time sequencing; Cancer attractor
• Online Access: http://link.springer.com/article/10.1186/s13045-020-00941-y

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.