Iron balance is critical for healthy and effective erythropoiesis and thrombopoiesis. All mammalian cells rely on iron and the erythropoietic compartment consumes especially high quantities of iron for hemoglobin synthesis. Effective crosstalk is essential for optimal red cell and platelet production. This session will discuss how heme and iron deficiency, excess, trafficking, and processing contribute to ineffective erythropoiesis and anemia and contribute to red cell and platelet production in JAK2 mutant myeloproliferative neoplasms.

Dr. Jan Abkowitz will present single cell transcriptomic and CITE-seq analyses of effective (normal) erythropoiesis and of the ineffective erythropoiesis seen in Diamond Blackfan anemia and MDS-5q. Most erythropoiesis takes place within erythroblastic islands (EBIs) comprised of a central macrophage (“nurse cell”) and 10-50 adjacent erythroid precursors. Dr. Abkowitz’s lab has recently isolated EBIs from human marrow and characterized their central macrophages at single cell resolution. She will describe how this cell normally functions as a safe and ecologically-efficient heme-iron recycler and how its dysfunction may contribute to MDS-5q anemia.

Dr. Radek Skoda will discuss the effects of iron availability on the phenotype of mouse models of myeloproliferative neoplasms (MPNs) driven by either JAK2-V617V or a N542-E543del mutation in JAK2 exon 12 (E12). While JAK2-V617F can manifest as polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis, expression of E12 results in PV, often with pure erythrocytosis phenotype. At baseline, PV patients with JAK2-V617V and JAK2-V617V mouse models with PV phenotype display iron deficiency, while ET patients and mice with an ET-like phenotype have normal iron stores. Dr. Skoda will describe the effects of iron deficiency and iron overload on the iron-responsive progenitor stages that decide between erythroid and megakaryocytic lineage choices and compare the effects of orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 on hemoglobin and iron parameters in JAK2-V617F and E12 mutant mouse models.