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

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the r...

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Bibliographic Details
Published in:Journal of cellular physiology 2024-02, Vol.239 (2), p.e31129-n/a
Main Authors: Xing, Tong, Yao, Wei‐Li, Zhao, Hong‐Yan, Wang, Jing, Zhang, Yuan‐Yuan, Lv, Meng, Xu, Lan‐Ping, Zhang, Xiao‐Hui, Huang, Xiao‐Jun, Kong, Yuan
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Adult
Aged
Aged, 80 and over
Bone marrow
Bone Marrow - pathology
Disorders
Flow cytometry
Hematopoiesis
Hematopoietic stem cells
Hemopoiesis
Humans
Infections - pathology
Inflammation
Leukemia
Leukemia, Myeloid, Acute - genetics
Leukemia, Myeloid, Acute - pathology
Leukocyte migration
Macrophages
Macrophages - pathology
Middle Aged
Monocytes
Myelodysplastic syndrome
Myelodysplastic syndromes
Myelodysplastic Syndromes - genetics
Phagocytosis
Risk
Stem cells
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Summary:Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective hematopoiesis. Accumulating evidence has shown that macrophages (MΦs) are important components in the regulation of tumor progression and hematopoietic stem cells (HSCs). However, the roles of bone marrow (BM) MΦs 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) MΦs/alternatively activated (M2) MΦs ratio in the BM of patients with higher‐risk MDS compared to lower‐risk MDS. BM MФs from patients with higher‐risk MDS and AML showed impaired phagocytosis activity but increased migration compared with lower‐risk MDS group. AML BM MΦs showed markedly higher S100A8/A9 levels than lower‐risk MDS BM MΦs. More importantly, coculture experiments suggested that the HSC supporting abilities of BM MΦs from patients with higher‐risk MDS decreased, whereas the malignant cell supporting abilities increased compared with lower‐risk MDS. Gene Ontology enrichment comparing BM MΦs from lower‐risk MDS and higher‐risk MDS for genes was involved in hematopoiesis‐ and immunity‐related pathways. Our results suggest that BM MΦs are involved in ineffective hematopoiesis in patients with MDS, which indicates that repairing aberrant BM MΦs may represent a promising therapeutic approach for patients with MDS.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.31129