In 2021, it was estimated that 1.92 billion people around the world struggle with anemia.1 However, anemia is more than a mere statistic, with its profound impact on health spanning all stages of life. Increased risk of preterm labor, low birthweight, impaired cognitive development in children, and increased risk for hospitalization and higher mortality in adults are just a few of the far-reaching consequences. Acknowledging that the reach of the solutions must be as broad as the problem, the 2024 Presidential Symposium, provided a vital platform to explore advancements in understanding red blood cell (RBC) physiology, ineffective erythropoiesis, and potential therapeutic interventions.
A Global Challenge
Mohandas Narla, DSc, the 2024 ASH president, selected the past, present, and future of RBC biology as the topic for the symposium. In curating the lineup, he emphasized the desire to “showcase ASH’s diversity in both gender and subject matter expertise.” The symposium featured three distinguished speakers who delivered clinically relevant discoveries in RBC biology — from membrane function to erythroid differentiation and metabolism.
Membrane Function
Patrick G. Gallagher, MD, from Nationwide Children’s Hospital, emphasized the pivotal role of the RBC membrane in maintaining cell integrity and functionality. “Novel treatment strategies in development offer hope for patients with many inherited and acquired erythrocyte disorders,” Dr. Gallagher said. His talk explored how mutations disrupt erythrocyte structural proteins, leading to hereditary membrane disorders such as spherocytosis and elliptocytosis. Genome-wide screening has made it possible to identify these disorders at an earlier age and with greater precision, paving the way for individualized approaches to treatment for these membranopathies. According to Dr. Gallagher, “novel treatment strategies in development offer hope for patients with many inherited and acquired erythrocyte disorders.” For example, pyruvate kinase activators are showing promise in improving energy balance and cell longevity in patients with red cell membrane disorders. Dr. Gallagher’s discussion underscored the need for continued research to translate these findings into routine clinical practice “It's exciting times,” he said. “There is a renaissance in erythroid cell biology research.”
Metabolism: The Engine of Erythropoiesis
Naomi Taylor, MD, from the National Institutes of Health, discussed the critical role of metabolism in erythroid lineage commitment and terminal differentiation. Her presentation focused on the complex process of metabolic reprogramming and its role in addressing disordered and ineffective erythropoiesis. Conditions like sideroblastic anemia and myelodysplastic syndromes (MDS) serve as examples. Dr. Taylor reviewed the biology of metabolite transporters in the context of their role in supplying the energy necessary for erythrocyte differentiation. She also discussed the impact of isocitrate dehydrogenase mutations in MDS, which present a novel opportunity for targeted metabolic interventions. Through the modulation of these metabolic pathways, researchers aim to restore effective erythropoiesis, to effectively address anemia in patients with metabolic red cell disorders.
Regulating Ineffective Erythropoiesis
Olivier Hermine, MD, PhD, from the IMAGINE Institute in Paris, explored the fine balance between erythroid differentiation and cell death. Dr. Hermine discussed the mechanisms that determine whether erythroid precursors successfully mature or undergo apoptosis, a process significantly impacted in hemoglobinopathies and MDS. In diseases such as thalassemia and sickle cell disease, disruptions in these pathways lead to ineffective erythropoiesis, exacerbating anemia. Gene therapies and small molecule inhibitors specifically aimed at promoting erythroid differentiation have the potential to suppress ineffective erythropoiesis. By addressing the underlying mechanisms directing the fate of erythroid precursors, another biologically informed strategy has emerged to target the complex anemia associated with ineffective erythropoiesis.
Bridging Science and Care
The symposium highlighted the vast innovations in red cell research and the mechanistic strategies emerging from diverse biological discoveries to treat anemia. By transforming research into actionable therapies, these advances are poised to benefit the nearly 2 billion individuals globally who contend with the spectrum of anemia-related disorders.
REFERENCE
- GBD 2021 Anaemia Collaborators. Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021. Lancet Haematol. 2023;10(9):e713-e734.
