Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood mononuclear cells after chemotherapy

单细胞转录组分析揭示化疗后急性髓系白血病外周血单核细胞的免疫细胞异质性

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作者:Xuqiao Hu #, Dongyan Cao #, Zhenru Zhou, Zhaoyang Wang, Jieying Zeng, Wen-Xu Hong

Conclusion

Our results elucidated the PBMC single-cell landscape and provided insights into precision medicine and immunotherapy for treating AML.

Methods

In this study, we used single-cell RNA sequencing (scRNA-seq) to analyse the PBMC microenvironment from five AML patients treated with different chemotherapy regimens and six healthy donors. We compared the cell compositions in AML patients and healthy donors, and performed gene set enrichment analysis (GSEA), CellPhoneDB, and copy number variation (CNV) analysis.

Purpose

Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the rapid clonal expansion of abnormally differentiated myeloid progenitor cells residing in a complex microenvironment. However, the immune cell types, status, and genome profile of the peripheral blood mononuclear cell (PBMC) microenvironment in AML patients after chemotherapy are poorly understood. In order to explore the immune microenvironment of AML patients after chemotherapy, we conducted this study for providing insights into precision medicine and immunotherapy of AML.

Results

Using scRNA-seq technology, 91,772 high quality cells of 44,950 PBMCs from AML patients and 46,822 PBMCs from healthy donors were classified as 14 major cell clusters. Our study revealed the sub-cluster diversity of T cells, natural killer (NK) cells, monocytes, dendritic cells (DCs), and haematopoietic stem cell progenitors (HSC-Prog) in AML patients under chemotherapy. NK cells and monocyte-DCs showed significant changes in transcription factor expression and chromosome copy number variation (CNV). We also observed significant heterogeneity in CNV and intercellular interaction networks in HSC-Prog cells.

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