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Cancer Cell International
Published in: Cancer Cell International 1/2024

Open Access 01-12-2024 | Acute Myeloid Leukemia | Research

Uncovering the cellular and omics characteristics of natural killer cells in the bone marrow microenvironment of patients with acute myeloid leukemia

Authors: Leisheng Zhang, Yunyan Sun, Chun-e Xue, Shuling Wang, Xianghong Xu, Chengyun Zheng, Cunrong Chen, Dexiao Kong

Published in: Cancer Cell International | Issue 1/2024

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Abstract

Background

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy and the most frequently acute leukemia of stem cell precursors and the myeloid derivatives in adult. Longitudinal studies have indicated the therapeutic landscape and drug resistance for patients with AML are still intractable, which largely attribute to the deficiency of detailed information upon the pathogenesis.

Methods

In this study, we compared the cellular phenotype of resident NK cells (rAML-NKs, rHD-NKs) and expanded NK cells (eAML-NKs, eHD-NKs) from bone marrow of AML patients (AML) and healthy donors (HD). Then, we took advantage of the co-culture strategy for the evaluation of the in vitro cytotoxicity of NK cells upon diverse tumor cell lines (e.g., K562, Nalm6, U937). With the aid of RNA-sequencing (RNA-SEQ) and bioinformatics analyses (e.g., GOBP analysis, KEGG analysis, GSEA, volcano plot), we verified the similarities and differences of the omics features between eAML-NKs and eHD-NKs.

Results

Herein, we verified the sharp decline in the content of total resident NK cells (CD3−CD56+) in rAML-NKs compared to rHD-NKs. Differ from the expanded eHD-NKs, eAML-NKs revealed decline in diverse NK cell subsets (NKG2D+, CD25+, NKp44+, NKp46+) and alterations in cellular vitality but conservations in cytotoxicity. According to transcriptomic analysis, AML-NKs and HD-NKs showed multifaceted distinctions in gene expression profiling and genetic variations.

Conclusions

Collectively, our data revealed the variations in the cytobiological and transcriptomic features between AML-NKs and HD-NKs in bone marrow environment. Our findings would benefit the further development of novel biomarkers for AML diagnosis and NK cell-based cytotherapy in future.
Appendix
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Metadata
Title
Uncovering the cellular and omics characteristics of natural killer cells in the bone marrow microenvironment of patients with acute myeloid leukemia
Authors
Leisheng Zhang
Yunyan Sun
Chun-e Xue
Shuling Wang
Xianghong Xu
Chengyun Zheng
Cunrong Chen
Dexiao Kong
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2024
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-024-03300-w

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