Evaluation of serum hepcidin concentrations in cancer and leukemia patients

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20581 Background: Hepcidin controls iron homeostasis by regulating iron uptake and redistribution in response to systemic iron requirements: high circulating iron leads to hepcidin expression which in turn decreases circulating iron. Hepcidin can also be induced by inflammation, which may lead to inappropriately low circulating iron levels, as seen in functional iron deficiency, a proposed causative factor in the anemia of inflammation. This study aimed to establish the hepcidin concentrations and hence the potential role of functional iron deficiency in contributing to anemia in cancer and leukemia patient populations. Methods: Sera from the following populations were analyzed: chemotherapy-induced anemia (CIA, n=100), anemia of cancer (AoC, n=30), sepsis (n=25), myelodysplastic syndrome (MDS, n=8), healthy controls (n=60), iron deficiency anemia (IDA, n=12), acute myeloid leukemia (AML, n=13), acute lymphoblastic leukemia (ALL, n=4), chronic myeloid leukemia (CML, n=10), multiple myeloma (MM, n=8) and chronic lymphocytic leukemia (CLL, n=11). Serum hepcidin concentrations were assessed by a sensitive, quantitative HPLC-MS/MS method. Iron indices and CRP (as an inflammatory marker) were also measured. Results: Serum hepcidin was elevated in a subset of patients with CIA (84±86ng/ml), AoC (100±97ng/ml), sepsis (189±204ng/ml), MDS (238±159ng/ml) and leukemia (223±203ng/ml). Serum hepcidin was not elevated in healthy donors (7±19ng/ml) or patients with IDA (9±14ng/ml). Further analysis of leukemia patient sera revealed elevated serum hepcidin in all patients with AML (354±153ng/ml) and ALL (532±266ng/ml), a spectrum of hepcidin concentrations within CML (156±179ng/ml) and MM (162±112ng/ml) patient populations. Hepcidin concentrations were elevated in CLL patients (59±29ng/ml), albeit to a lesser degree than observed in the other subsets evaluated. In some patient populations, elevated CRP and hepcidin concentrations were both present. Conclusions: This study demonstrates that hepcidin concentrations are elevated in multiple cancer and leukemia patient populations raising the possibility that functional iron deficiency may play a role in the etiology of anemia in cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc.