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

• Published in: Cancer cell international Vol. 24; no. 1; pp. 106 - 13
• Main Authors: Zhang, Leisheng, Sun, Yunyan, Xue, Chun-e, Wang, Shuling, Xu, Xianghong, Zheng, Chengyun, Chen, Cunrong, Kong, Dexiao
• Format: Journal Article
• Language: English
• Published: England BioMed Central 14.03.2024; BMC
• Subjects: Acute myeloid leukemia; Acute myeloid leukemia (AML); Antibodies; Apoptosis; Bioinformatics; Biomarkers; Blood cancer; Bone marrow; Bone marrow microenvironment; CD25 antigen; CD3 antigen; CD56 antigen; Cell culture; Cell cycle; Cellular vitality; Cytokines; Cytotoxicity; Drug resistance; Epigenetics; Flow cytometry; Gene expression; Genetic diversity; Genetic engineering; Hematology; Leukemia; Malignancy; Microenvironments; Mutation; Natural killer (NK) cells; Natural killer cells; NKG2 antigen; Omics analysis; Phenotypes; Software; Transcriptomics; Tumor cell lines; United States > US; China; Omics analysis; Cellular vitality; Natural killer (NK) cells; Acute myeloid leukemia (AML); Bone marrow microenvironment
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-024-03300-w

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. 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. 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. 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.