Myelofibrosis (MF) may be caused by various pathogenic mechanisms such as 
elevation in circulating cytokine levels, cellular interactions and genetic 
mutations. However, the underlying mechanism of MF still remains unknown. Recent 
studies have revealed that fibrocytes, the spindle-shaped fibroblast-like 
hematopoietic cells, and the thrombopoietin (TPO)/myeloproliferative leukemia 
protein (MPL; TPO receptor) signaling pathway play a certain role in the 
development of MF. In the present study, we aimed to investigate the 
relationship between fibrocytes and MPL activation. We showed that TPO or a TPO 
receptor agonist directly induces fibrocyte differentiation using murine 
fibrocyte cell lines and a murine MF model. Conversely, elimination of 
macrophages expressing MPL by clodronate liposomes reversed the MF phenotype of 
the murine model, suggesting that fibrocyte differentiation induced by MPL 
activation contributes to the progression of MF. Furthermore, we revealed that 
SLAMF7high MPLhigh monocytes in human peripheral blood mononuclear cells were 
possible fibrocyte precursors and that these cells increased in number in MF 
patients not treated with ruxolitinib. Our findings confirmed a link between 
fibrocytes and the TPO/MPL signaling pathway, which could result in a greater 
understanding of the pathogenesis of MF and lead to the development of novel 
therapeutic interventions.