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World J Clin Oncol. Oct 24, 2026; 17(10): 126647
Published online Oct 24, 2026. doi: 10.5306/wjco.126647
Characterization of the cellular and transcriptomic landscapes of natural killer cells in hematopoietic microenvironment of myelodysplastic syndrome
Su-Yun Liu, Xiu-Mei Feng, Zi-Ying Chen, Zhi-Qiang Chen, Yu-Ru Shang, Michael Linnebacher, Yuan-Xin Wang, Shan-Shan Zhang, Min Cai, Lei-Sheng Zhang
Su-Yun Liu, Department of Pediatric Internal Medicine, Pingxiang People’s Hospital, Pingxiang 337000, Jiangxi Province, China
Xiu-Mei Feng, Zi-Ying Chen, Zhi-Qiang Chen, Yuan-Xin Wang, Shan-Shan Zhang, Min Cai, Lei-Sheng Zhang, Shandong Provincial Key Medical and Health Laboratory of Blood Ecology and Biointelligence, Jinan Key Laboratory of Medical Cell Bioengineering, Science and Technology Innovation Center, The Fourth People’s Hospital of Jinan Affiliated to Shandong Second Medical University, Jinan 250031, Shandong Province, China
Zi-Ying Chen, Zhi-Qiang Chen, Faculty of Pharmacy, Medical College, Qingdao University, Qingdao 266071, Shandong Province, China
Yu-Ru Shang, Michael Linnebacher, Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Rostock 18057, Mecklenburg-Vorpommern, Germany
Yu-Ru Shang, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen 518055, Guangdong Province, China
Co-first authors: Su-Yun Liu and Xiu-Mei Feng.
Author contributions: Liu SY and Feng XM conducted sample collection, manuscript writing, and they contributed equally to this work as co-first authors; Chen ZY, Chen ZQ, Shang YR, Linnebacher M, Wang YX, and Zhang SS conducted the data analyses and interpretation, manuscript writing, and revision; Cai M and Zhang LS conceived and designed the study, and gave final approval of the manuscript. All authors have read and approved the publication of the manuscript.
AI contribution statement: No AI tools were used in the preparation of this manuscript.
Supported by Natural Science Foundation of Shandong Province, No. ZR2025MS1382; Taishan Scholar Special Funding of Shandong Province Funding, No. tsqnz20240858; Science and Technology Development Plan of Jinan Municipal Health Commission, No. 2025202005; Medical and Health Technology Project of Shandong Province, No. 202402050122; and Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau, No. 202430055.
Institutional review board statement: The study was conducted with the approval of the Ethics Committee of The Fourth People’s Hospital of Jinan Affiliated to Shandong Second Medical University and the guideline of Helsinki Declaration (approval No. LL20240077 and No. LL20240071).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data of the study are included in the published article. Meanwhile, the relative datasets are available from corresponding author upon reasonable request.
Corresponding author: Lei-Sheng Zhang, PhD, Professor, Senior Researcher, Shandong Pro
vincial Key Medical and Health Laboratory of Blood Ecology and Biointelligence, Jinan Key Laboratory of Medical Cell Bioengineering, Science and Technology Innovation Center, The Fourth People’s Hospital of Jinan Affiliated to Shandong Second Medical University, No. 50 Shifan Road, Tianqiao District, Jinan 250031, Shandong Province, China.
kczxzls@jn.shandong.cn
Received: August 11, 2026
Revised: September 6, 2026
Accepted: October 8, 2026
Published online: October 24, 2026
Processing time: 73 Days and 23.7 Hours
BACKGROUND
Myelodysplastic syndrome (MDS) is a common hematological malignancy, which gradually worsens in patients with chronic cytopenias owing to progressive bone marrow (BM) failure and/or transformation into acute myeloid leukemia.
AIM
To verify the systematic and detailed information of natural killer (NK) cell-mediated pathogenesis in the BM microenvironment.
METHODS
Herein, we enriched BM mononuclear cells from 19 MDS patients and 19 healthy donors (HD), and analyzed the immunophenotype and content of the corresponding resident NK cells (rMDS-NKs, rHD-NKs) using flow cytometry analysis and cell counting. Then, we utilized our well-established “3ILs”-based (rhIL-2, rhIL-15, rhIL-18) strategy for ex vivo amplification and dissection of the expanded NK cells (eMDS-NKs, eHD-NKs). Cell apoptosis and cell cycle analyses were conducted for the comparison of cellular viability, and coculture with diverse tumor cell lines was employed for cytotoxicity assessment. Besides cellular analysis, we performed RNA-sequencing and multifaceted bioinformatics analyses for transcriptomic signature evaluation of eMDS-NKs and eHD-NKs, including gene expression profiling and genetic spectrum.
RESULTS
As to resident NK cells in BM mononuclear cells, resident MDS-NKs showed significant decline in the content of NKG2D+ activated and CD25+ memory-like NK cell subsets, while minimal differences were observed in total NK cells (CD3-CD56+), total activated NK cells (CD3-CD56+CD16+) or relative activated NK cell subsets (NKp44+, NKp46+). As to expanded NK cells after 14-day’s culture, eMDS-NKs revealed impaired amplification and decrease in the contents of the indicated NK cell subsets (CD25+, NKp44+, NKp46+). Meanwhile, the variations in cellular viability and cytotoxicity were identified, particularly the alterations in cell cycle of eMDS-NKs compared to eHD-NKs. Furthermore, the similarities and diversities of gene expression pattern and genetic spectrum of eMDS-NKs and eHD-NKs were also verified.
CONCLUSION
Collectively, our data indicated the multidimensional alterations and the concomitant conservations of MDS-NKs compared to HD-NKs both at the cellular and transcriptomic levels. These findings would provide novel references for further illuminating the NK cell-mediated pathogenesis of MDS and facilitating the development of diagnostic and therapeutic options for MDS in future.
Core Tip: Myelodysplastic syndrome (MDS) are myeloid malignancies of hematopoietic stem cells with limited treatment options. Longitudinal studies have highlighted the tumor microenvironment and dysregulated immune response in MDS, yet the pathogenesis of natural killer cells (NKs) are largely obscure. Therewith, we dissected the biological and transcriptomic signatures of NKs in bone marrow of MDS patients, which would facilitate the further exploration of MDS-NK-meditated pathogenesis and treatment options in future.
