Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (10): 32-40.doi: 10.6040/j.issn.1671-7554.0.2021.0725

Previous Articles     Next Articles

Characteristics of bone marrow immune microenvironment in patients with acute myeloid leukemia based on single-cell RNA sequencing

WANG Yan1, ZHANG Yuhui1, HU Naibo1, TENG Guangshuai1, ZHOU Yuan2, BAI Jie1   

  1. 1. Department of Hematology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China;
    2. State Key Laboratory of Experimental Hematology, Institute of Hematology &
    Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Chinese Academy of Medical Sciences &
    Peking Union Medical College, Tianjin 300020, China
  • Published:2021-10-15

PDF (PC)

278

Abstract: Objective To analyze the composition of bone marrow immune microenvironment in patients with acute myeloid leukemia(AML)by single cell sequencing technology, and to explore the role of different subsets of different types of immune cells in the occurrence and development of AML. Methods The scRNA-seq data(GSE116256)which met the requirements of this study were downloaded from GEO database and processed with the Seurat package of R language. The cell subsets were annotated by single R package and reference to previous studies, the proportion of different types of immune cells was calculated, and the differentially expressed genes(DEGs)of cell subsets between AML patients and normal controls were calculated. Gene ontology function annotation(GO)and Kyoto Encyclopedia of genes and genomes(KEGG)enrichment analysis on DEGs were performed to clarify the role of cell subsets in the progression of AML. Results Compared with the normal control group, AML patients had changed proportion of progenitor cells, monocytes, NK/T cells, dendritic cells and B cells. GO analysis indicated that the proliferation, differentiation, immune regulation and killing function of monocytes, dendritic cells, B cells and T cells were damaged. Conclusion There are big differences in the immune microenvironment between AML patients and healthy people, and these differences may be closely related to the occurrence and development of AML.

Key words: Acute myeloid leukemia, Single cell sequencing, Bone marrow microenvironment, Immune cells, Bioinformatics

CLC Number: 

  • R551.3
[1] Creutzig U, Kutny MA, Barr R, et al. Acute myelogenous leukemia in adolescents and young adults [J]. Pediatr Blood Cancer, 2018, 65(9): e27089.
[2] 张静, 何欢, 曾雪倩, 等. 急性髓系白血病耐药相关信号通路的研究进展[J]. 河北医学, 2021, 27(1): 167-170. ZHANG Jing, HE Huan, ZENG Xueqian, et al. Research progress on drug resistance related signaling pathways in acute myeloid leukemia [J]. Hebei Medicine, 2021, 27(1): 167-170.
[3] Cai SF, Levine RL. Genetic and epigenetic determinants of AML pathogenesis [J]. Semin Hematol, 2019, 56(2): 84-89.
[4] Nahas MR, Stroopinsky D, Rosenblatt J, et al. Hypomethylating agent alters the immune microenvironment in acute myeloid leukaemia(AML)and enhances the immunogenicity of a dendritic cell/AML vaccine [J]. Br J Haematol, 2019, 185(4): 679-690.
[5] Webster JA, Pratz KW. Acute myeloid leukemia in the elderly: therapeutic options and choice [J]. Leuk Lymphoma, 2018, 59(2): 274-287.
[6] Ma P, Xing M, Han L, et al. High PDL1 expression drives glycolysis via an Akt/mTOR/HIF1alpha axis in acute myeloid leukemia [J]. Oncol Rep, 2020, 43(3): 999-1009.
[7] Kamitani I, Saito T, Yokoyama H, et al. Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation [J]. J Infect Chemother, 2021, 27(4): 639-641.
[8] Cheng Y, Wang X, Qi P, et al. Tumor microenvironmental competitive endogenous RNA network and immune cells act as robust prognostic predictor of acute myeloid leukemia [J]. Front Oncol, 2021, 11: 584884. doi: 10.3389/fonc.2021.584884.
[9] Chen HJ, Zhang S, Luo QD, et al. Research advance on the immune escape of acute myeloid leukemia—review [J]. J Exp Hematol, 2020, 28(4): 1429-1432.
[10] Leimkuhler NB, Schneider RK. Inflammatory bone marrow microenvironment [J]. Hematology Am Soc Hematol Educ Program, 2019, 2019(1): 294-302.
[11] Bruck O, Blom S, Dufva O, et al. Immune cell contexture in the bone marrow tumor microenvironment impacts therapy response in CML [J]. Leukemia, 2018, 32(7): 1643-1656.
[12] Guo R, Lu M, Cao F, et al. Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment [J]. Biomark Res, 2021, 9(1): 15.
[13] Petti AA, Williams SR, Miller CA, et al. A general approach for detecting expressed mutations in AML cells using single cell RNA-sequencing [J]. Nat Commun, 2019, 10(1): 3660.
[14] Miles LA, Bowman RL, Merlinsky TR, et al. Single-cell mutation analysis of clonal evolution in myeloid malignancies [J]. Nature, 2020, 587(7834): 477-482.
[15] van Galen P, Hovestadt V, Wadsworth IM, et al. Single-Cell RNA-Seq Reveals AML Hierarchies Relevant to Disease Progression and Immunity[J]. Cell, 2019,176(6):1265-1281.
[16] Kantarjian HM, Kadia TM, DiNardo CD, et al. Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach [J]. Cancer, 2021, 127(8): 1186-1207.
[17] 刘姚姚, 杨福军, 刘超, 等. 骨髓微环境调控白血病干细胞的研究进展[J]. 现代肿瘤医学, 2018, 26(21): 3520-3523. LIU Yaoyao, YANG Fujun, LIU Chao, et al. Research progress of bone marrow microenvironment regulating leukemia stem cells [J]. Journal of Modern Oncology, 2018, 26(21): 3520-3523.
[18] Ugel S, Cane S, De Sanctis F, et al. Monocytes in the TUMOR Microenvironment [J]. Annu Rev Pathol, 2021, 16: 93-122. doi: 10.1146/annurev-pathmechdis-012418-013058.
[19] Shen CK, Huang BR, Yeh WL, et al. Regulatory effects of IL-1beta in the interaction of GBM and tumor-associated monocyte through VCAM-1 and ICAM-1 [J]. Eur J Pharmacol, 2021, 905: 174216. doi: 10.1016/j.ejphar.2021.174216.
[20] 江楚怡, 蔡晶, 王泽华, 等. 人类肿瘤中Tie2阳性单核巨噬细胞研究进展[J]. 肿瘤防治研究, 2021, 48(3): 314-318. JIANG Chuyi, CAI Jing, WANG Zehua, et al. Tie2 expressing monocytes/macrophages in human tumors [J]. Cancer Research on Prevention and Treatment, 2021, 48(3): 314-318.
[21] Anguille S, Van de Velde AL, Smits EL, et al. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia [J]. Blood, 2017, 130(15): 1713-1721.
[22] 何易祥, 赵宇昊, 高昭, 等. B淋巴细胞及相关细胞因子在骨免疫系统中对破骨细胞分化的作用[J]. 中国组织工程研究, 2021, 25(29): 4709-4714. HE Yixiang, ZHAO Yuhao, GAO Zhao, et al. Effect of B lymphocytes and related cytokines on osteoclast differentiation in the osteoimmunology system [J]. Chinese Journal of Tissue Engineering Research. 2021, 25(29): 4709-4714.
[23] Oh DY, Kwek SS, Raju SS, et al. Intratumoral CD4+T cells mediate anti-tumor cytotoxicity in human bladder cancer [J]. Cell, 2020, 181(7): 1612-1625.
[24] Li H, van der Leun AM, Yofe I, et al. Dysfunctional CD8+T Cells form a proliferative, dynamically regulated compartment within human melanoma [J]. Cell, 2019, 176(4): 775-789.
[1] LIU Teng, MA Yingchun. Expression of ECT2 in uterine corpus endometrial carcinoma and its clinical significance based on bioinformatics database [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 63-71.
[2] LI Yanru, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin. Proteomic analysis of serum exosomes in pancreatic cancer with different stages of progress [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 33-41.
[3] ZHANG Zhaoying, MA Chunhong. Immunomodulatory effects of bile acid in hepatointestinal diseases [J]. Journal of Shandong University (Health Sciences), 2021, 59(9): 30-36.
[4] QIAO Chong, WANG Tingting. Research progress of maternal-fetal immunomodulatory mechanism [J]. Journal of Shandong University (Health Sciences), 2021, 59(8): 24-31.
[5] ZHANG Xiaohui, LUO Jianmin, SUO Xiaohui, SUN Guofeng, LI Jing. Relationship between methylation of tumor suppressor genes SOCS1 and SOCS3 and remission and prognosis of 80 acute myeloid leukemia patients [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 67-73.
[6] HUA Fang, ZHANG Weiwei, LYU Bo, XIN Wei. Bioinformatic analysis of genes and molecular pathways associated with osteoarthritis synovitis [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 10-17.
[7] LI Canxuan, CHEN Jie. Expression and activity mechanism of acetyl-CoA acyltransferase 1 in clear cell renal cell carcinoma based on bioinformatics [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 26-33.
[8] LI Yinglin, SONG Daoqing, XU Zhonghua. Identification of FKBP11 expression in clear cell renal cell carcinoma using bioinformatics analysis [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 45-51.
[9] TIAN Baorui, ZHANG Yongchao, HAN Xiaoyang, TIAN Yingying, WANG Chuanxi. Prediction of the association between genes and glioblastoma based on databases [J]. Journal of Shandong University (Health Sciences), 2020, 58(6): 8-13.
[10] DAI Xiaoyu, LU Yuan, WANG Zhiheng, LI Mingzhuo, SI Shucheng, LI Jiqing, JING Ming, XUE Fuzhong. Value of blood routine data in distinguishing myelodysplastic syndrome and acute myeloid leukemia [J]. Journal of Shandong University (Health Sciences), 2020, 58(1): 20-25.
[11] WANG Jianxiang, GU Runxia. Advances in targeted therapy for acute myeloid leukemia [J]. Journal of Shandong University (Health Sciences), 2019, 57(7): 6-12.
[12] ZHOU Jian, ZHAO Hanting, LÜ Gang, WANG Lin, LI Qihang, ZHU Meiyan, WANG Zhilin, HE Shenyi. Bioinformatics analysis and construction of an eukaryocyte vector of ROP19 protein in Toxoplasma gondii [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(3): 64-69.
[13] YANG Juan, QIU Zongjian, SONG Qiang. Impacts of Simvastatin on DNA methyltransferase of cell line NB4 in acute myeloid leukemia [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2015, 53(6): 28-32.
[14] YUAN Shoudao, WANG Fengqin, ZHANG Jiao, ZHAO Weiming, Jason J. Chen. Mass spectrometry analysis of proteins differentially expressed between adenocarcinoma and squamous carcinoma of the cervix [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(8): 14-21.
[15] YIN Dong-mei1, XU Hong-zhi1, ZHANG Jing-yao1, SUI Xiao-hui1, CUI Bin2, MA Chun-yan2, ZHEN Chang-qing1. Changes and clinical significances of CD4+T cell subsets in aplastic anemia,
myelodysplastic syndromes and acute myeloid leukemia patients [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(3): 66-70.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] WANG Huan-liang,SUN Bao-zhu,DU Hong-mei,ZHOU Chang-qing,ZHANG Li. Controlling the depth of propofol anesthesia using the bispectral indexand the systolic blood pressure[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(5): 471 -474 .
[2] SONG Yong-hong,MA Chun-hong,LV Hong-juan,ZHU Chuan-fu,NIE Xiang-min,WANG Mei,LIU Yan,ZHANG Ping. HLA allele polymorphism in northern Hans of China[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(6): 546 -553 .
[3] YU Hui1,2, CHEN Shaohua1, ZHAO Jiajun2, GAO Ling3
. Effects of ethanol on glycogen content, GSK3β，
and PAMPK of L02 cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(04): 75 -78 .
[4] HOU Xiao-yang,BU Pei-li,ZHANG Yun,FENG Jin-bo,LIU Chun-xi,LI Chuan-bao,HAO Ming-xiu. Peroxisome proliferatorsactivated receptor α play a critical role in the inhibition of myocardial fibrosis induced by AngⅡ in vitro[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(7): 665 -668 .
[5] HUANGQing,TIAN Hui,LI Lin,LIANG Fei,LIU Xi-xian. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(6): 556 -559 .
[6] ZHU Mei-jia,HAN Ju,WANG Xin-yi,LU Wei,WANG Ai-hua,GUAN Xin-hua,CAO Xia,CAO Bing-zhen. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(8): 834 -839 .
[7] . Susceptibilityweighted imaging of diffuse axonal injury: a correlative
study of lesionnumber and Glasgow Score Scale[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(10): 126 -129 .
[8] ZENG Ji-ping,WANG Li-na,WANG Li-xiang,REN Xiao-hui,ZHANG Meng-ye,XIA Wen,CUI Xing. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(5): 467 -470 .
[9] SHU Ya,QI Feng. Jaw thrust device (JTD) on obesity patients for maintaining the airway patency during general anesthesia induction[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 1072 -1074 .
[10] ZHAO Zheng-bin1， XUE Shuang-lin2， ZHANG Li-ting1， LI Jun-feng1，ZHAO Rong-rong1， ZHOU Hai-lian3， CHEN Hong1. Effects of procyanidins on the proliferation of hepatic stellate cells and production of TIMP-1 induced by leptin[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(7): 46 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd