Resident bone marrow macrophages provide a microenvironment for erythropoiesis, forming erythroblastic islands (EBIs) via adhesion molecules. In this study, we examined vascular cell adhesion molecule-1 (VCAM-1) expression in human bone marrow specimens using immunohistochemistry. VCAM-1 was strongly expressed in CD169 + macrophages in EBIs and weakly in sinusoidal vascular endothelial cells. In reactive erythropoiesis, including hemolytic and megaloblastic anemia, the extended cytoplasm of

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... -1 + CD169 + macrophages circumscribed the erythroid cells. The strong affinity between VCAM-1 + macrophages and erythroid cells was also observed in polycythemia vera (PV), essential thrombocythemia (ET), and chronic myelogenous leukemia (CML). VCAM-1 density was significantly higher in PV than in ET and CML (p < 0.001), and correlated with blood erythrocyte count in all three neoplasms (p < 0.001). In ET, the VCAM-1 density was higher in cases with the JAK2 mutation than with the CALR mutation. In myelodysplastic syndrome with erythroid predominance but unclear EBI formation, punctate VCAM-1 + cytoplasmic processes of macrophages were seen between erythroblasts, similar to those seen between granulocytic precursors in CML, suggesting incomplete contact of VCAM-1 + macrophages with dysplastic erythroid cells. These results suggest that VCAM-1 + macrophages create a niche for reactive and neoplastic erythropoiesis and may be a therapeutic target in PV.