Bone marrow macrophages are involved in the ineffective hematopoiesis of myelodysplastic syndromes

被引:0
作者
Xing, Tong [1 ,2 ]
Yao, Wei-Li [1 ]
Zhao, Hong-Yan [1 ]
Wang, Jing [1 ]
Zhang, Yuan-Yuan [1 ]
Lv, Meng [1 ]
Xu, Lan-Ping [1 ]
Zhang, Xiao-Hui [1 ]
Huang, Xiao-Jun [1 ,2 ]
Kong, Yuan [1 ]
机构
[1] Peking Univ, Natl Clin Res Ctr Hematol Dis, Beijing Key Lab Hematopoiet Stem Cell Transplantat, Peoples Hosp,Inst Hematol,Collaborat Innovat Ctr H, Beijing, Peoples R China
[2] Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划; 北京市自然科学基金;
关键词
bone marrow; hematopoiesis; macrophages; myelodysplastic syndromes; ENDOTHELIAL-CELL FUNCTION; STEM-CELLS; MICROENVIRONMENT; MONOCYTES; NICHES;
D O I
10.1002/jcp.31129
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (M phi s) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) M phi s in regulating normal and malignant hematopoiesis in different clinical stages of MDS are largely unknown. Age-paired patients with lower-risk MDS (N = 15), higher-risk MDS (N = 15), de novo acute myeloid leukemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. Flow cytometry analysis showed increased pro-inflammatory monocyte subsets and a decreased classically activated (M1) M phi s/alternatively activated (M2) M phi s ratio in the BM of patients with higher-risk MDS compared to lower-risk MDS. BM MCYRILLIC CAPITAL LETTER EFs from patients with higher-risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower-risk MDS group. AML BM M phi s showed markedly higher S100A8/A9 levels than lower-risk MDS BM M phi s. More importantly, coculture experiments suggested that the HSC supporting abilities of BM M phi s from patients with higher-risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower-risk MDS. Gene Ontology enrichment comparing BM M phi s from lower-risk MDS and higher-risk MDS for genes was involved in hematopoiesis- and immunity-related pathways. Our results suggest that BM M phi s are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM M phi s may represent a promising therapeutic approach for patients with MDS.
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页数:14
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共 41 条
  • [1] Myelodysplastic syndromes
    Ades, Lionel
    Itzykson, Raphael
    Fenaux, Pierre
    [J]. LANCET, 2014, 383 (9936) : 2239 - 2252
  • [2] Induction of myelodysplasia by myeloid-derived suppressor cells
    Chen, Xianghong
    Eksioglu, Erika A.
    Zhou, Junmin
    Zhang, Ling
    Djeu, Julie
    Fortenbery, Nicole
    Epling-Burnette, Pearlie
    Van Bijnen, Sandra
    Dolstra, Harry
    Cannon, John
    Youn, Je-in
    Donatelli, Sarah S.
    Qin, Dahui
    De Witte, Theo
    Tao, Jianguo
    Wang, Huaquan
    Cheng, Pingyan
    Gabrilovich, Dmitry I.
    List, Alan
    Wei, Sheng
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (11) : 4595 - 4611
  • [3] Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche
    Chow, Andrew
    Lucas, Daniel
    Hidalgo, Andres
    Mendez-Ferrer, Simon
    Hashimoto, Daigo
    Scheiermann, Christoph
    Battista, Michela
    Leboeuf, Marylene
    Prophete, Colette
    van Rooijen, Nico
    Tanaka, Masato
    Merad, Miriam
    Frenette, Paul S.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (02) : 261 - 271
  • [4] Niches that regulate stem cells and hematopoiesis in adult bone marrow
    Comazzetto, Stefano
    Shen, Bo
    Morrison, Sean J.
    [J]. DEVELOPMENTAL CELL, 2021, 56 (13) : 1848 - 1860
  • [5] Modulation of tumor-associated macrophages in colitis-associated colorectal cancer
    Dong, Yingjie
    Yang, Qiuli
    Niu, Ruiying
    Zhang, Zhiyuan
    Huang, Yijin
    Bi, Yujing
    Liu, Guangwei
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2022, 237 (12) : 4443 - 4459
  • [6] B cells and macrophages pursue a common path toward the development and progression of chronic lymphocytic leukemia
    Galletti, G.
    Caligaris-Cappio, F.
    Bertilaccio, M. T. S.
    [J]. LEUKEMIA, 2016, 30 (12) : 2293 - 2301
  • [7] CD14+ cells from peripheral blood positively regulate hematopoietic stem and progenitor cell survival resulting in increased erythroid yield
    Heideveld, Esther
    Masiello, Francesca
    Marra, Manuela
    Esteghamat, Fatemehsadat
    Yagci, Nurcan
    von Lindern, Marieke
    Migliaccio, Anna Rita F.
    van den Akker, Emile
    [J]. HAEMATOLOGICA, 2015, 100 (11) : 1396 - 1406
  • [8] M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors
    Huo, Yi
    Zhang, Han
    Sa, Longqi
    Zheng, Wenjing
    He, Yang
    Lyu, Haohan
    Sun, Mengjie
    Zhang, Lingling
    Shan, Lequn
    Yang, Angang
    Wang, Tao
    [J]. JOURNAL OF TRANSLATIONAL MEDICINE, 2023, 21 (01)
  • [9] Atorvastatin enhances bone marrow endothelial cell function in corticosteroid-resistant immune thrombocytopenia patients
    Kong, Yuan
    Cao, Xie-Na
    Zhang, Xiao-Hui
    Shi, Min-Min
    Lai, Yue-Yun
    Wang, Yu
    Xu, Lan-Ping
    Chang, Ying-Jun
    Huang, Xiao-Jun
    [J]. BLOOD, 2018, 131 (11) : 1219 - 1233
  • [10] Leimkühler NB, 2019, HEMATOL-AM SOC HEMAT, P294, DOI 10.1182/hematology.2019000045