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.

Applications of single-cell sequencing in cancer research: progress and perspectives

“…The accumulation of increasingly abundant single-cell sequencing data enabled establishment of The Cancer Cell Atlas, which covers a spectrum of cancers (Table 2 ). For example, Microwell-Seq contributed to cellular hierarchy construction and clonal heterogeneity deciphering in normal bone marrow and acute myeloid leukemia [ 69 ]. By integrating clinical pathological information and single-cell sequencing data, novel diagnostic and prognostic biomarkers and potential therapeutically relevant cell types or states could be deciphered [ 70 ].…”

Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

“…In this study, we characterized the immune components of different AML patient-derived BM cells by sc-RNAseq data analysis. Different from concentrating on analysis of clonal heterogeneity and hierarchies of AML cells [ 31 , 32 ], we focused on the mature immune cell types and immune status under the stress of AML and chemotherapy. To assess the composition, function, and status of immune cells, we performed scRNA-seq analysis using publicly-available datasets (GSE116256) [ 32 ].…”

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

“…Acute myeloid leukemia (AML) is a disease which is characterized by clonal proliferation and is derived from primitive hematopoietic stem cells or progenitor cells. It has an extremely high mortality and poor prognosis in elderly patients (116,117). Cytogenetic analysis revealed that there are a large number of non-random chromosomal abnormalities in AML, with about 60% of adult AML patients being diagnosed with gene abnormalities (118).…”