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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2020

Open Access 01-12-2020 | Acute Myeloid Leukemia | Research

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

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

Published in: Journal of Hematology & Oncology | Issue 1/2020

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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.
Appendix
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Metadata
Title
A single-cell survey of cellular hierarchy in acute myeloid leukemia
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
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2020
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-020-00941-y

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