Single-cell transcriptomic profiling reveals immune cell heterogeneity in acute myeloid leukaemia peripheral blood
Xuqiao Hu1,2, Dongyan Cao3,4, Zhenru Zhou5,6
1Shenzhen Center for Chronic Disease Control and Prevention, Shenzhen Institute of Dermatology, Shenzhen, China. haniahu@hotmail.com.
Insights
This study used single-cell RNA sequencing to analyze the immune microenvironment of acute myeloid leukemia (AML) patients post-chemotherapy. Findings reveal significant changes in immune cell profiles, offering insights for precision medicine and immunotherapy.
Area of Science:
- Immunology
- Genomics
- Oncology
Background:
- Acute myeloid leukemia (AML) is a complex disease with a poorly understood immune microenvironment after chemotherapy.
- Peripheral blood mononuclear cells (PBMCs) play a crucial role in the AML microenvironment.
Purpose of the Study:
- To explore the immune cell landscape and genomic profiles of PBMCs in AML patients post-chemotherapy.
- To provide insights for developing precision medicine and immunotherapy strategies for AML.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on PBMCs from five AML patients and six healthy donors.
- Comparative analysis of cell composition, gene set enrichment analysis (GSEA), CellPhoneDB, and copy number variation (CNV) analysis were conducted.
Main Results:
- scRNA-seq classified over 138,000 cells into 14 major clusters, revealing sub-cluster diversity in T cells, NK cells, monocytes, dendritic cells (DCs), and hematopoietic stem cell progenitors (HSC-Prog).
- Significant alterations in transcription factor expression and CNV were observed in NK cells and monocyte-DCs.
- HSC-Prog cells exhibited notable heterogeneity in CNV and intercellular interaction networks.
Conclusions:
- The study elucidated the single-cell PBMC landscape in AML patients undergoing chemotherapy.
- These findings offer valuable insights for advancing precision medicine and immunotherapy in AML treatment.
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.
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.
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.
Conclusion:
Our results elucidated the PBMC single-cell landscape and provided insights into precision medicine and immunotherapy for treating AML.
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