Hepcidin Is Produced by Lymphoplasmacytic Cells and Is Associated With Anemia in Waldenström's Macroglobulinemia

Waldenström's macroglobulinemia (WM) patients often present with anemia as their primary disease manifestation that may be related to hepcidin, an important regulator of iron homeostasis. We therefore determined hepcidin levels in 53 WM patients, and 20 age-matched healthy patient donors by hepcidin-25 ELISA. Serum hepcidin levels were elevated in WM patients versus healthy patients (P = .04), and correlated with BM disease involvement (P = .004), beta-2-microglobulin levels (P = .029), and inversely with hemoglobin (P = .05). No correlation with serum iron indices was observed, though in patients with high hepcidin levels, increased iron deposition in bone marrow macrophages was observed. Importantly, hepcidin transcripts and protein were produced by primary WM cells. Hepcidin levels correlated with serum IL-6 (P < .001) and C-Reactive Protein (P = .033) levels. The results of this study implicate hepcidin as a contributor to anemia in WM, and suggest that an iron re-utilization defect accompanies hepcidin overproduction leading to its sequestration in WM patients.