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Newly Discovered Functions of Megakaryocytes and Platelets

PhD Trainee
Program: Scientific Symposia
Hematology Disease Topics & Pathways:
Bleeding disorders, Bleeding and Clotting, Diseases, Biological Processes
Sunday, December 8, 2024: 4:30 PM-5:45 PM
Room 29 (San Diego Convention Center)
Chair:
Alessandra Balduini, MD, Tufts University
Disclosures:
No relevant conflicts of interest to declare.

This session will explore cutting-edge discoveries in platelet biogenesis and the pathological mechanisms underlying platelet-related disorders.

Key topics include the role of glycosylation in megakaryocyte (Mk) and platelet (PLT) functions and their involvement in disease. Focus will be placed on the role of sialic acid and galactose modifications in regulating megakaryocyte-primed hematopoietic stem cell function and megakaryocyte activity, especially in relation to thrombocytopenia, including immune thrombocytopenias. Additionally, novel insights into thrombo-inflammation will be discussed, highlighting how inflammatory processes contribute to thrombosis and platelet dysfunction. Emerging research on the role of megakaryocytes and platelets in bone marrow fibrosis will also be featured, shedding light on their dual function in both hematopoiesis and pathological fibrosis. These topics are highly relevant, particularly with ongoing advancements in understanding the basic mechanisms of platelet production, glycosylation, and the interaction between thrombosis and inflammation.

Dr. Karin Hoffmeister will discuss the role of sialic acid and galactose modifications in regulating megakaryocyte activity. These glycan decorations are crucial for maintaining proper megakaryocyte function and platelet production, with disruptions contributing to platelet clearance and immune-mediated destruction in conditions like immune thrombocytopenia (ITP).

Dr. Tobias Petzold will discuss novel insights on natural occurring resilience mechanism to prevent thromboinflammation as key pathomechanism in thrombotic diseases. By introducing the concept of long-term immobility induced thromboprotection we will learn from a novel animal model- the hibernating brown bear - that is protected from developing venous thrombosis during 6 months of immobility in winter.  These findings will be translated into the clinical context.

Dr. Anna Nam will discuss the impact of ER stress and the unfolded protein response on megakaryopoiesis and platelets due to mutations in CALR in essential thrombocythemia and myelofibrosis. Using advanced single-cell multi-omics approaches, we show that CALR mutations elicit the unfolded protein response in human. Targeting ER stress-related pathways leads to reduction in platelet burden in mouse models.

Karin M. Hoffmeister, MD

Versiti Blood Research Institute, Milwaukee, WI, Milwaukee, WI

Tobias Petzold, MD, MSc

Klinik für Kardiologie, Angiologie und Intensivmedizin, Charité – Universitätsmedizin Berlin, Berlin, Germany

Anna S. Nam, MD

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY

See more of: Scientific Symposia