Fig. 2
From: Momelotinib: an emerging treatment for myelofibrosis patients with anemia
Momelotinib suppresses hepcidin expression in hepatocytes via inhibition of the BMP6/ACVR1/SMAD and IL-6/JAK/STAT3 pathways. Hepcidin is elevated in MF patients due to aberrant hyperactivation of the BMP6-stimulated kinase ACVR1/ALK2 signaling and inflammatory cytokine signaling via IL-6, which is also elevated in MF patients. Suppression of hepcidin expression in the liver increases circulating iron [Tf-(Fe3+)2] and hemoglobin; and stimulates erythropoiesis in the bone marrow. Abbreviations: ACVR1 activin A receptor type 1, BMP bone morphogenetic protein, BMP2 bone morphogenetic protein 2, BMP6 bone morphogenetic protein 6, BMP RE BMP response element, HAMP hepcidin gene, HFE homeostatic iron regulator, HJV hemojuvelin, IL-6 interleukin-6, JAK Janus kinase, LSECs liver sinusoidal endothelial cells, MMB momelotinib, SMAD small-mothers-against-decapentaplegic, STAT3 signal transducer and activator of transcription 3, STAT3 RE STAT3 response element, Tf transferrin, TfR1 transferrin receptor-1, TfR2 transferrin receptor-2, TMPRSS6 Transmembrane protease, serine 6