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Understanding Iron and Red Blood Cell Metabolism

November 23, 2022

Chair, ASH Scientific Committee on Iron and Heme; Professor of Medicine, Department of Pathology and Laboratory Medicine at UCLA, Los Angeles, CA

“One day, everything will be iron.” This is not a statement of imperial ambition on the part of our committee; it refers to the exceptional stability of iron nuclei that is causing iron to accumulate in the universe, at the expense of other less stable elements. Its reactive electron cloud makes iron an efficient biological catalyst and an essential trace nutrient. Erythrocytes contain most of the iron and heme in the body, and iron and heme are central to erythrocyte physiology and pathology. The strong historical connection between hematology and iron biology provides important context for the work of our committee.

The Scientific Committee on Iron and Heme is focused on all aspects of normal and pathological iron metabolism and heme synthesis relevant to blood cells and their progenitors on the cellular, organ, and organismal level. Our field is unusual in its interdisciplinary orientation, and some of us work closely with colleagues in gastroenterology, hepatology, nephrology, obstetrics and gynecology, nutrition, and public health. Our committee members ( represent well our diverse interests, scientific and medical backgrounds, and geographical origins. Our closest thematic neighbor, the Scientific Committee on Red Cell Biology, shares our interest in red cell biology, but our focus is specifically on erythroid iron and heme pathways, control of iron availability for erythropoiesis, and regulatory roles for heme and iron in erythrocyte development and metabolism.

The past 25 years have been revolutionary for our field. We’ve progressed from classical erythroid and iron physiology to the molecular definition of iron and heme transporters and the mechanisms that regulate cellular iron uptake. We better understand storage and intracellular iron trafficking, and can identify the hormones and receptors that control systemic absorption and distribution of iron. We succeeded in identifying the molecular lesions that underlie many of the diseases under our purview including iron-refractory iron deficiency anemia, hereditary and acquired microcytic anemias, anemia of inflammation, porphyrias, and hemochromatosis. The newly described pathways have been rapidly targeted for diagnostic and therapeutic applications. Many laboratories around the globe have made important contributions, and our scientific area is known as a welcoming and sharing community.

Particularly active areas of research include iron sensing for systemic iron homeostasis, iron transport across membranes, subcellular iron and heme trafficking, dietary heme absorption, the toxicology of iron and heme, the role of iron and heme in regulating inflammation, and tissue- and organ-autonomous regulation of local iron metabolism. Continuing priorities for translational research include the development of less toxic iron chelators, exploration of iron-restrictive therapies for hemoglobinopathies and polycythemia vera, and understanding the mechanisms and impact of iron deficiency in pregnancy and postnatal development, infection, and chronic disease processes, including heart failure and chronic kidney disease. In view of the global impact of iron deficiency, especially on women, children, and older adults, the potential dangers of iron supplementation in areas with endemic malaria and enteric infections, research on improved diagnosis and treatment of iron deficiency remains an important part of our agenda.

Finally, we have a track record of embracing unexpected scientific, technical, and clinical developments. This is not only important for keeping the ASH annual meeting program fresh, relevant, and exciting, but also for attracting talented trainees and new investigators who can move our agenda forward.

Scientific Committee on Iron and Heme: Iron and Red Cells: A Co-Dependent Relationship

In the largest organismal iron flow, macrophages recycle iron from senescent erythrocytes for delivery to erythropoietic marrow where iron is incorporated into heme in hemoglobin of new erythrocytes. This session will present recent advances in the study of mechanisms of iron recycling and discuss the profound influence of malaria on the genetic evolution of such mechanisms.

Tomas Ganz, MD, PhD, University of California, Los Angeles, Los Angeles, CA

Shang Ma, PhD, Scripps Research, San Diego, CA
Piezo1 in Anemia and Iron Overload

Robin Van Bruggen, MD, PhD, Sanguin, Amsterdam, the Netherlands
Iron Recycling in the Spleen

Sarah H. Atkinson, MD, The London School of Hygiene & Tropical Medicine, London, United Kingdom
Anemia and Iron Homeostasis in Malaria

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