Hepcidin and multiple myeloma related anemia.
Multiple myeloma (MM) is a B cell lymphoproliferative disorder in which malignant plasma cells accumulate in the bone marrow and usually produce monoclonal immunoglobulin in excess. Interleukin-6 (IL-6), is known to be an essential survival factor of myeloma cells, high IL-6 levels being correlated with an adverse prognosis. IL-6 modulates the transcription of several liver-specific acute phase protein genes, including C-reactive protein and hepcidin. Anemia is one of the prominent features of MM, along with recurrent osteolytic lesions, bacterial infections and renal insufficiency. The current treatment strategies of MM related anemia are often inadequate and many patients rely on transfusions. Several causes have been implicated, but anemia of chronic disease (ACD) related to the inflammatory cytokines appears to be one of the main culprits. The pathogenesis of ACD had been poorly understood, but recently it has been shown that increased Il-6 upregulates the hepatic production of hepcidin, which, by binding to its cellular receptor, ferroportin, causes anemia by blocking iron export from enterocytes and macrophages. We hereby argue that by virtue of its biological characteristics, multiple myeloma should be an ideal clinical setting to test the role of hepcidin in the pathogenesis of ACD. Hepcidin levels should be higher in MM patients and might correlate with prognosis. Anemic MM patients should also be among those who would benefit mostly from hepcidin targeted therapies.
Cucuianu
Andrei
A
Department of Hematology, University of Medicine and Pharmacy, Bvd 21 Decembrie Nr 73, Cluj-Napoca, Romania. acucuianu@yahoo.com
Patiu
Mariana
M
Rusu
Anca
A
D000740:Anemia / Q000150:complications / Q000503:physiopathology*; D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D064451:Hepcidins; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D009101:Multiple Myeloma / Q000150:complications / Q000503:physiopathology*
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D015850:Interleukin-6