Blood Podcast Key role of hepcidin in polycythemia vera, signatures of CAR T cell dysfunction, and IL-34 as a novel AML therapy?
Jun 29, 2023
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Hepcidin Levels Drive Polycythemia Vera Severity
- Hepcidin centrally controls PV severity by restricting iron availability, and low hepcidin (eg HFE variants) amplifies JAK2V617F-driven erythrocytosis.
- In mice, deleting hepcidin worsened PV while antisense targeting TMPRSS6 (raising hepcidin) ameliorated disease and reduced need for phlebotomy.
Consider Hepcidin Mimetics As A Treatment Strategy
- Consider hepcidin mimetics as a therapeutic strategy to withhold iron and reduce erythrocytosis in PV; rusfertide is already in clinical trials.
- Further trials must confirm efficacy, safety, and cost-effectiveness versus routine phlebotomy.
HFE Variants And Inflammation Modify PV Through Hepcidin
- In GWAS and Finnish cohorts, hemochromatosis-associated HFE variants that reduce hepcidin were overrepresented in PV, linking iron regulation genetics to disease risk.
- Patient plasma and IL-6–family cytokines induced hepatocyte hepcidin expression, implicating inflammation-driven hepcidin upregulation in PV.