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Hematology Disease Topics & Pathways:
Research, Fundamental Science, Hemoglobinopathies, Diseases, Myeloid Malignancies, Biological Processes
Description:
Ineffective erythropoiesis is the leading cause of red cell-related diseases, including anemia, which stands as the most prevalent hematologic disease, affecting millions of individuals worldwide. Understanding the underlying mechanisms of ineffective erythropoiesis is pivotal for advancing diagnostic and therapeutic approaches in hereditary anemias and adult-onset conditions. This session will explore recent breakthroughs in research related to ineffective erythropoiesis, focusing on areas of hemoglobinopathies, malaria infection, and myeloid neoplasms. By bringing together experts at the forefront of these investigations, the session will not only enhance understanding of the pathogenesis of ineffective erythropoiesis but also catalyze the development of innovative approaches to treat related diseases.
Dr. El Nemer will discuss the molecular mechanisms underlying ineffective erythropoiesis in beta thalassemia (bTM) major and sickle cell disease (SCD). The talk will draw a parallel between bTM and SCD to describe the cellular dysfunctions observed in both pathologies involving the chaperon protein HSP70 and oxidative stress. The talk will also discuss the impact of ineffective erythropoiesis on the erythroid and hematopoietic niches in SCD.
Dr. Egan will discuss the impact of Plasmodium falciparum malaria on erythropoiesis. In malaria infection, P. falciparumparasites invade and replicate within human erythrocytes in the peripheral blood, leading to anemia, microvascular congestion, and multi-organ dysfunction. Emerging evidence suggests that erythroblastic islands in the bone marrow also serve as a critical reservoir for parasites, which may contribute to malaria anemia. Recent investigations into host cell responses to P. falciparum infection of erythroid precursor cells derived ex-vivo from primary human hematopoietic stem/progenitor cells (HSPCs) identified stage-specific transcriptional changes in infected cells, including in genes involved in cell cycle regulation, stress responses, and key developmental processes. Efforts employing scRNA-seq and mass cytometry to elucidate molecular interactions between P. falciparum and the hematopoietic niche at single-cell resolution and their potential implications for erythropoiesis will be discussed.
Dr. Doulatov will discuss advances in understanding how splicing factor mutations in SF3B1 drive ineffective erythropoiesis and hematopoiesis in myelodysplastic syndromes. Recent development of induced pluripotent stem cell models and precise gene editing of primary human hematopoietic stem cells have provided insights into splicing alterations induced by mutant SF3B1 and their functional impact on hematopoiesis and erythropoiesis. Due to its essential role in disease pathophysiology, therapeutic strategies for targeting mutant SF3B1 will also be discussed.
Dr. El Nemer will discuss the molecular mechanisms underlying ineffective erythropoiesis in beta thalassemia (bTM) major and sickle cell disease (SCD). The talk will draw a parallel between bTM and SCD to describe the cellular dysfunctions observed in both pathologies involving the chaperon protein HSP70 and oxidative stress. The talk will also discuss the impact of ineffective erythropoiesis on the erythroid and hematopoietic niches in SCD.
Dr. Egan will discuss the impact of Plasmodium falciparum malaria on erythropoiesis. In malaria infection, P. falciparumparasites invade and replicate within human erythrocytes in the peripheral blood, leading to anemia, microvascular congestion, and multi-organ dysfunction. Emerging evidence suggests that erythroblastic islands in the bone marrow also serve as a critical reservoir for parasites, which may contribute to malaria anemia. Recent investigations into host cell responses to P. falciparum infection of erythroid precursor cells derived ex-vivo from primary human hematopoietic stem/progenitor cells (HSPCs) identified stage-specific transcriptional changes in infected cells, including in genes involved in cell cycle regulation, stress responses, and key developmental processes. Efforts employing scRNA-seq and mass cytometry to elucidate molecular interactions between P. falciparum and the hematopoietic niche at single-cell resolution and their potential implications for erythropoiesis will be discussed.
Dr. Doulatov will discuss advances in understanding how splicing factor mutations in SF3B1 drive ineffective erythropoiesis and hematopoiesis in myelodysplastic syndromes. Recent development of induced pluripotent stem cell models and precise gene editing of primary human hematopoietic stem cells have provided insights into splicing alterations induced by mutant SF3B1 and their functional impact on hematopoiesis and erythropoiesis. Due to its essential role in disease pathophysiology, therapeutic strategies for targeting mutant SF3B1 will also be discussed.