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 (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.