Scientific Program

CARs for Kids: Chimeric Antigen Receptor T-cell Therapy for Childhood Leukemias

Scientific Committee on Blood Disorders in Childhood

Saturday, December 6, 2025, 2:00 p.m. - 3:15 p.m. OCCC - Tangerine Ballroom F3-4

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape of pediatric leukemias, achieving remission rates in children with otherwise refractory disease. Yet, despite its promise, significant challenges remain in achieving durable remissions, expanding efficacy beyond B-cell malignancies, and safely applying this approach across diverse leukemia subtypes. This session will explore the latest translational and clinical advances driving the next generation of CAR-T therapies for childhood leukemias. Together, the talks featured in this session will provide a forward-looking view of how cutting-edge CAR-T innovations are reshaping pediatric leukemia treatment—from B-acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML)—and paving the way toward broader, more durable cures.

Dr. Sara Ghorashian will review clinical outcomes in relapsed and refractory B-cell ALL and discuss novel strategies to enhance CAR-T efficacy, mitigate relapse, and evaluate the potential for introducing CAR-T earlier in therapy.

Dr. Maksim Mamonkin will address the unique challenges of developing CAR-T therapy for T-cell ALL. His presentation will highlight innovative antigen-targeting approaches, and engineering strategies to overcome T-cell self-death and aplasia, and the most recent results from emerging clinical trials that signal progress in this difficult leukemia subtype.

Dr. Paulina Velasquez will focus on solutions to two critical barriers in AML: antigen heterogeneity and the immunosuppressive tumor microenvironment. She will discuss dual-targeted CAR constructs and preclinical immunocompetent models designed to optimize therapeutic efficacy.

Chair:

Julie Jaffray, MD
Rady Children's Hospital, University of California, San Diego
San Diego, CA, United States

Speakers:

Sara Ghorashian, FRCPath, PhD
Great Ormond Street Institute of Child Health
London, ENG, United Kingdom
CAR T-Cell Breakthroughs: Shaping the Future of B-Cell ALL Treatment

Maksim Mamonkin, PhD
Baylor College of Medicine
Houston, TX, United States
T-Cell ALL Meets CAR-T: Advancements and Breakthroughs

Paulina Velasquez, MD
St. Jude Children's Hospital
Memphis, TN, United States
Harnessing CAR-T: A New Era in AML Treatment

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Dissecting Enhancer Function in Hematopoietic Development and Disease

Scientific Committee on Epigenetics and Genomics

Saturday, December 6, 2025, 9:30 a.m. - 10: 45 a.m. OCCC - W312

New developments in 3-D functional genomics, genetic manipulation, and systems approaches in computational biology are enabling the dissection of cis-regulatory elements at unprecedented resolution. These techniques are uncovering new aspects of enhancer biology and function, including discrete regulatory elements within individual enhancers and super-enhancers. This session will highlight recent findings stemming from these innovative techniques in the activity of enhancers in regulating gene expression in normal and malignant hematopoiesis. Attendees will learn how these cutting-edge approaches are informing our understanding of hematopoietic transcriptional regulation in normal and disease states.

Dr. Anders Hansen will present recent findings from the use of ultra-high-resolution 3D genomics to map how DNA interactions change across red blood cell development, revealing the dynamics of chromatin loops and boundaries with gene activity. He will discuss how novel enhancer-promoter interactions are enriched with erythroid transcription factors and how these interactions help link fetal hemoglobin regulation to loci implicated in genome-wide association studies.

Dr. Martin Rivas will discuss how enhancers control normal lymphoid development and immune cell formation, and how their disruption or hijacking through mechanisms such as chromosomal translocations and chromatin modifier mutations drives lymphoma development and progression. His talk will also explore how targeting these aberrant enhancer activities presents promising new therapeutic strategies for treating lymphoma.

Dr. Mira Kassouf will introduce "facilitators," a newly identified type of regulatory element that, unlike classical enhancers, lack intrinsic enhancer activity but are essential for enhancers to fully activate target genes. Using the alpha-globin enhancer as a model, the research demonstrates that facilitators are interchangeable yet display functional hierarchy based on their position, potentially creating functional polarity within multi-part super-enhancers. This work raises important questions about how facilitators potentiate enhancer activity and how the regulatory landscape syntax modulates gene expression.

Chair:

Megan McNerney, MD, PhD
The University of Chicago
Chicago, IL, United States

Speakers:

Anders Hansen
MIT Biological Engineering
Cambridge, MA, United States
Imaging and Systems Biology Approaches For Studying Enhancer Activity

Martin Rivas, PhD, MS
University of Miami
Miami, FL, United States
Enhancer Function in Lymphoid Development and Lymphoma

Mira Kassouf
Oxford University
OXFORD, ENG, United Kingdom
Multi-partite Enhancer Assembly and Chromatin Architecture

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Exploring the Origins of Multiple Myeloma: Germline Predisposition and Early Deregulations

Scientific Committee on Plasma Cell Neoplasia

Saturday, December 6, 2025, 9:30 a.m. - 10: 45 a.m. OCCC - West Hall D1

This session will explore the earliest biological and genetic events that underly the development of multiple myeloma (MM), from inherited predisposition to the emergence of malignant plasma cells. By integrating germline genetics, cellular hierarchies, and early molecular and immune deregulations, the presentations will collectively address the continuum from predisposition to disease initiation and progression. Advances in genomic technologies and single-cell approaches now enable detailed characterization of both inherited risk factors and early cellular events that shape disease evolution. Understanding these processes is critical not only for elucidating MM pathogenesis but also for defining opportunities for early detection, prevention, and ultimately cure.

Dr. Celine Vachon will discuss germline genetic variants associated with susceptibility to MM, encompassing both rare and common alleles that influence precursor states such as monoclonal gammopathy of undetermined significance (MGUS). She will review how inherited variation contributes to inter-individual differences in disease risk and progression from MGUS to overt MM, providing new insights into genetic predisposition and molecular epidemiology.

Dr. Rodger Tiedemann will present recent findings on the identification and characterization of MM progenitor populations, including malignant B cells and pre-plasma cells. He will describe how these rare populations may harbor the full spectrum of clonal aberrations found in plasma cells, persist through therapy, and contribute to relapse. The lack of target antigen expression, such as BCMA, GPRC5D, or CD38 on progenitor MM cells, underscores their potential role in treatment resistance and disease recurrence.

Dr. Romanos Sklavenitis-Pistofidis will focus on early molecular and immune deregulations in MGUS and smoldering MM. He will highlight tumor-intrinsic alterations and microenvironmental dysfunction that drive transformation, emphasizing how integrating molecular and immune profiling can inform early interception strategies.

Chair:

Salomon Manier, MD, PhD
Lille University Hospital
Lille, N/A, France

Speakers:

Celine Vachon, PhD
Mayo Clinic
Rochester, MN, United States
Germline Genetic Variants and Predisposition to Multiple Myeloma

Rodger Tiedemann, MD, PhD
University of Aukland
Auckland, New Zealand
Identifying and Characterizing the Cells of Origin in Multiple Myeloma

Romanos Sklavenitis-Pistofidis, MD
Dana-Farber Cancer Institute
Boston, MA, United States
Early Molecular and Immune Deregulations in Premalignant Conditions

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Flipping the Switch: Fetal Hemoglobin Reactivation for Treating Hemoglobin Disorders – From Mechanism to Therapy

Scientific Committee on Red Cell Biology

Saturday, December 6, 2025, 2:00 p.m. - 3:15 p.m. OCCC - Sunburst Room (W340)

Fetal hemoglobin (HbF) reactivation is a validated therapeutic strategy for hemoglobinopathies such as sickle cell disease and β-thalassemia. By reducing sickle hemoglobin (HbS) polymerization or increasing total hemoglobin levels, HbF reactivation can effectively mitigate disease. BCL11A, a central HbF repressor, is a genetically and clinically validated target. Advances in genome editing technologies now enable precise disruption of BCL11A erythroid enhancers or direct editing of fetal globin promoters, offering the potential for durable, one-time treatments. This session will highlight recent insights into hemoglobin gene regulation, novel HbF reactivation strategies, and the latest progress in gene therapies for hemoglobin disorders.

Dr. Merlin Crossley will present recent work on the identification and characterization of new regulators of hemoglobin switching, with a particular focus on transcriptional regulators and epigenetic complexes involved in globin gene regulation. The talk will open with a brief update on the current state of the field.

Dr. Daniel Bauer will discuss the application of genome editing technologies for HbF reactivation, reviewing both preclinical and clinical data. He will describe current approaches with ex vivo cell product manufacturing and myeloablative chemotherapy and future opportunities to simplify delivery and expand patient access.

Dr. Giuliana Ferrari will discuss advances in clinical gene therapy for hemoglobinopathies. Recent studies reveal that the intrinsic properties of hematopoietic stem cells (HSCs) and the altered bone marrow microenvironment in β-thalassemia play critical roles in disease biology and therapeutic response. She will highlight cellular and molecular differences between thalassemic and normal HSCs, shaped by signals from the diseased niche, as well as transcriptional profiling of gene therapy-treated patients in relation to clinical outcomes.

Chair:

Jian Xu, PhD
St. Jude Children's Research Hospital
Memphis, TN, United States

Speakers:

Merlin Crossley, PhD
School of Biotechnology and Biomolecular Sciences
University of NSW, NSW, NSW, Australia
Identifying and Targeting New Regulators of Hemoglobin Switching

Daniel Bauer, MD, PhD
Harvard Medical School
Boston, MA, United States
Preclinical Development of Gene Editing Approaches for Hemoglobin Disorders

Giuliana Ferrari Jr, PhD
Istituto Scientifico H. San Raffaele
Milan, Italy, Italy
Developing Gene Therapy Approaches for Treating Hemoglobin Disorders

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Harnessing The Hemostasis Interactome for Novel Insights and Mechanisms of Coagulation Proteins

Scientific Committee on Hemostasis

Sunday, December 7, 2025, 9:30 a.m. - 10: 45 a.m. OCCC - W311EFGH

This session explores emerging paradigms in hemostasis through the lens of the “hemostasis interactome”—the complex network of coagulation proteins and their functional, structural, and regulatory partners. By integrating structural biology, activity-based biochemistry, and genetic modulation, this session will highlight innovative approaches to decipher the dynamic interplay that governs thrombin generation, anticoagulant regulation, and therapeutic modulation. Together, the talks in this session will illustrate how the hemostatic interactome can be harnessed to unravel mechanistic intricacies and inspire innovative treatments for bleeding and thrombotic disorders.

Dr. Enrico Di Cera, will spotlight cutting-edge cryo-electron microscopy studies that elucidate how factor Va (FVa) functions as both an essential cofactor in prothrombinase complex formation and as a substrate for proteolytic inactivation by activated protein C (APC). These structural insights uncover key conformational states of FVa, offering a molecular basis for understanding its dual roles in coagulation and anticoagulation.

Dr. Rodney Camire will delve into activity-guided discoveries of factor V’s diverse isoforms, with a focus on FV-short—a unique splice variant that exerts anticoagulant effects through interactions with tissue factor pathway inhibitor alpha (TFPIα) and APC. By dissecting patient-derived mutations and antibody studies, this presentation will reveal how FV acts as a molecular switch that can be selectively modulated to restore hemostatic balance.

Dr. Raja Prince-Eladnani will introduce a novel genetics-guided strategy to rebalance coagulation via RNA interference–mediated silencing of Protein S. This key anticoagulant hub engages TFPI, APC, and FIXa, and its inhibition restores thrombin generation in hemophilia models while improving long-term joint and bone outcomes. His talk will address mechanistic and translational implications of targeting Protein S as a non-replacement therapeutic strategy.

Chair:

Rinku Majumder, PhD
LSU Health Science Center
New Orleans, LA, United States

Speakers:

Enrico Di Cera, MD
Saint Louis University School of Medicine
St Louis, MO, United States
Unveiling the Hemostasis Interactome: A Structure-Guided Discovery of Blood's Hidden Secrets

Rodney Camire, PhD
University of Pennsylvania
Philadelphia, PA, United States
Unlocking the Hemostasis Interactome: Activity-Guided Discovery of Blood's Key Connections

Raja Prince-Eladnani Jr
Bern University Hospital, Inselspital
Bern, Switzerland
Decoding the Hemostasis Interactome: A Genetics-Guided Exploration of Blood’s Blueprint

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Innovative Models of Lymphoma

Scientific Committee on Lymphoid Neoplasia

Saturday, December 6, 2025, 2:00 p.m. - 3:15 p.m. OCCC - West Hall E2

The biology of lymphomas is complex, characterized by both genetic and non-genetic alterations in lymphoma cells, as well as perturbed crosstalk with the tumor microenvironment, all of which influence clinical course and treatment outcomes. Model systems are essential for elucidating these complex biological processes and the mechanisms driving lymphoma development, progression, and treatment resistance within a controlled and reproducible environment. Recent advancements in the field have significantly improved our ability to accurately model human lymphoma. The session "Innovative Models of Lymphoma" will provide a comprehensive overview of novel and innovative models increasingly available for studying lymphoma, with a particular emphasis on the tumor microenvironment. Overall, the session aims to enhance understanding of how these models can be optimally utilized to advance knowledge of lymphoma biology and treatment effects, facilitating the translation of research findings into clinical applications. The presentations will cover ex vivo and in vivo models, including refined lymphoma transplantation strategies and genetically engineered mouse models, focusing on their individual strengths and limitations.

Dr. Ankur Singh will present recent advancements in engineering synthetic ex vivo models of human lymphomas, including bioengineered lymphoid organoids informed by tumor microenvironment data, and explore how these models reveal mechanisms of therapy resistance and the role of tumor-immune interactions.

Dr. Michael Green will discuss the development and application of patient-derived xenograft models for studying large B-cell lymphoma, highlighting their molecular heterogeneity and their use in identifying factors that influence responses to small molecules and cellular therapies.

Dr. Wendy Beguelin will highlight the use of genetically engineered mouse models for studying genetically defined lymphoma subtypes within an immunocompetent setting, discussing their potential to recapitulate the natural progression of the disease and the challenges posed by their complex genetic alterations.

Chair:

Oliver Weigert, MD
Ludwig-Maximilians-University (LMU) Hospital
Munich, Germany

Speakers:

Ankur Singh
Georgia Institute of Technology
Atlanta, GA, United States
Bioengineering Synthetic Lymphoma Models: Advancements in Ex Vivo Systems

Michael R Green, PhD
MD Anderson Medical Center
Houston, TX, United States
Utilizing Refined Lymphoma Models for Treatment Studies: Innovations in Syngeneic Transplants, Patient-Derived Xenografts, and Humanized Mouse Model

Wendy Béguelin, PhD
Weill Cornell Medical College
New York, NY, United States
Genetically Engineered Mouse Models (GEMMs): Dissecting Subtype Specific Biologies

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Iron and Heme Metabolism and Its Considerations in Understanding Pathophysiology and Therapy

Scientific Committee on Iron and Heme

Saturday, December 6, 2025, 9:30 a.m. - 10: 45 a.m. Hyatt - Regency Ballroom OPQ

Iron dysregulation is frequently a consequence of hematopoietic disorders caused by genetic defects not directly related to iron. In hematopoietic conditions such as sickle cell diseases, patients are anemic but paradoxically have iron overload in storage tissues. Treating the iron overload or deficiency can significantly decrease morbidity and mortality and significantly increase quality of life. This session highlights basic science and clinical advances related to understanding and targeting iron dysregulation in managing hematopoietic conditions. The first talk highlights how mishandling of heme, the most abundant chemical form of iron in blood, can cause toxicity in organ systems and exacerbate the severity of sickle cell disease. The second talk takes on a clinical focus, discussing how iron dysregulation exacerbates the physiologic stress of pregnancy, and advances in diagnosing  and treating iron deficiency in this population. The third talk ends the session by highlighting how recent basic science advances in iron biology have catalyzed the development of genetic therapies for iron mislocalization or dysregulation in hematopoietic diseases. This session is timely because it ties together basic science studies from the “golden age of iron” and shows how these studies gave insight into the intersection between iron dysregulation and disease pathogenesis. The take-home message for the audience is that iron dysregulation can be a consequence of hematopoietic or physiological stress conditions, and targeting iron dysregulation can be an important adjunct to alleviating the severity of these conditions and may inform the standard of care in treatment.

Chair:

Yvette Yien, PhD
University of Pittsburgh
Pittsburgh, PA, United States

Speakers:

Samit Ghosh, PhD
Vascular Medicine Institute, University of Pittsburgh
Pittsburgh, PA, United States
Heme Trafficking and Its Role in Modifying Physiology and Hematopoietic Diseases

Michelle Sholzberg, MD
University of Toronto
Toronto, ON, Canada
Iron Deficiency/Overload and Its Considerations In Design of Therapeutic Strategies

Stefano Rivella, PhD
Children’s Hospital of Philadelphia
Philadelphia, PA, United States
Targeting Iron Deficiency/Overload as a Therapeutic Strategy in Treating Hematologic Disease

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JOINT SESSION: Game of Clones – The Evolution of Hematopoiesis from Birth to Aging

Scientific Committee on Hematopathology and Clinical Laboratory Hematology

Sunday, December 7, 2025, 9:30 a.m. - 11: 05 a.m. OCCC - W312

Aging of the blood system has widespread consequences from an increased risk of malignant transformation to reduced immune fitness. Many of these changes originate at the level of hematopoietic stem cells (HSCs). These cells evolve across the human lifespan, from their developmental origins to age-associated clonal expansion and disease. This session will highlight how genetic, epigenetic, and environmental influences shape clonal selection, fitness, and dysfunction in hematopoiesis.

Dr. Adam Mead will begin by examining evidence for a fetal origin of driver mutations that initiate myeloid malignancies. Using lineage-tracing and neonatal blood spot analyses, he will demonstrate that certain myeloid neoplasm mutations arise prenatally and that fetal hematopoiesis provides a permissive environment for their expansion. These developmental contexts establish lasting transcriptional and chromatin programs that define leukemia stem cell behavior and therapeutic vulnerabilities.

Dr. Grant Challen will follow with a discussion of how recurrent mutations in epigenetic regulators confer fitness advantages to HSCs. He will describe how these mutations alter the epigenome to disrupt normal stem cell regulation, promote clonal dominance under selective pressures, and influence human health during aging-associated clonal hematopoiesis.

Dr. Michael Milsom will then focus on the impact of aging and inflammation on hematopoietic stem cell integrity. He will discuss how infection and inflammatory signals accelerate molecular changes within the HSC compartment through emergency hematopoiesis, and how stem cell dormancy may mitigate clonal attrition.

Dr. Nancy Gillis will provide an overview of clonal hematopoiesis, emphasizing its epidemiology, clinical significance, and prognostic factors associated with progression to myeloid malignancies. She will highlight current gaps in understanding and management, encouraging discussion on how to translate emerging discoveries into clinical practice.

Chairs:

Peter van Galen, PhD
Brigham and Women´s Hospital
Boston, MA, United States

Ingo Ringshausen, MD
University College London
London, London, United Kingdom

Speakers:

Adam Mead, MBBChir
University of Oxford
Oxford, ENG, United Kingdom
Embryogenesis and Early Mutations in Hematopoietic Stem Cells

Grant Challen, PhD
Washington University
St Louis, MO, United States
Genetic-Epigenetic Regulators Providing a Competitive Advantage to HSCs

Michael Milsom, PhD
DKFZ, Heidelberg, Germary
Heidelberg, Germany
Inflammation and Expansion of Dysregulated Stem Cells

Nancy Gillis, PharmD, PhD
Moffitt Cancer Center
Tampa, FL, United States
Clonal Hematopoiesis: The Good, the Bad, and the Unknown

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JOINT SESSION: The Emerging Landscape of Germline Predisposition to Bone Marrow Failure and Leukemia

Scientific Committee on Bone Marrow Failure and Scientific Committee on Myeloid Neoplasia

Saturday, December 6, 2025, 4:00 p.m. - 5:35 p.m. Hyatt - Plaza Int'l HIJK

There is a rapid expansion in the discovery and characterization of factors underlying genetic predisposition to bone marrow failure and hematologic malignancy risk. The first talk will focus on recent studies using a genome-first approach to define the population prevalence of germline variants in genes causing inherited bone marrow failure syndromes (IBMFS) and leukemia predisposition syndromes and discuss the implications of this expanded recognition of prevalence on our understanding of clinical phenotypes at the population level. The next talk will discuss the mechanisms that underlie somatic clonal progression in IBMFS and how they inform our understanding of disease-specific malignancy risk. The lessons from IBMFS can also be translated to a more generalized understanding of the gene-specific and context-selective malignancy risk of sporadic clonal hematopoiesis, and the implications of recently defined paradigms in IBMFS on our understanding of clonal hematopoiesis in the general population will be discussed. The final talk will discuss the expanding understanding of DDX41 in leukemia pathogenesis, highlighting recently described molecular mechanisms. The focus will be on how aging-related bone marrow stress in patients with germline DDX41 loss-of-function mutations selects hematopoietic stem cells with "second-hit" DDX41 mutations, contributing to a bone marrow failure-like disorder and malignant progression despite low mutation abundance.

Speakers:

Lisa McReynolds
National Cancer Institute, National Institutes of Health
Bethesda, MD, United States
Inherited Susceptibility to Bone Marrow Failure and Leukemia is More Common Than you Think

R. Coleman Lindsley Jr, MD, PhD
Dana-Farber Cancer Institute
Boston, MA, United States
Beyond Malignancy: How Insights from IBMFS Inform Clonal Hematopoiesis Malignancy Risk More Broadly

Timothy Chlon, PhD
Cincinnati Children's Hospital
Cincinnati, OH, United States
Defining the Biology of DDX41

Pinkal Desai, MD, MPH
Weill Cornell Medical College
New York, NY, United States
Somatic Mutations may Precede Acute Myeloid Leukemia Even Years Before Diagnosis

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Mechanisms that Direct and Derail Lineage-Specific Gene Expression Programs in Myelopoiesis

Scientific Committee on Myeloid Biology

Monday, December 8, 2025, 2:45 p.m. - 4:00 p.m. OCCC - Valencia Room W415D

Normal myelopoiesis is driven by lineage-specific transcriptional programs established through multiple layers of regulation. The same mechanisms that define cell state-specific gene expression output are often misappropriated to drive malignancies. Both normal and malignant transcriptomes are shaped by the chromatin state, executed by transcription factor complexes during mRNA transcription, and refined post-transcriptionally through regulated access to translation machinery. This session will explore how recent fundamental discoveries have informed our understanding of the various mechanisms that go awry during abnormal myelopoiesis and malignancy, leading to novel translational opportunities.

Dr. Bruno Di Stefano will focus on the biogenesis of RNA processing bodies (P-bodies) and the role of specific RNA helicases in regulating the availability of select transcripts for protein translation. He will discuss the implications of this process for normal stem cell biology and how its aberrant reshaping contributes to myeloid malignancy.

Dr. Ulrich Steidl will cover mechanisms governing transcription and its impact on hematopoietic stem cell fate decisions, sub-clonal heterogeneity, and clonal evolution in normal, pre-leukemic, and malignant hematopoiesis, and how stochastic nature of transcription determines pre-malignant stem cell plasticity. He will also cover how these discoveries inform conceptually novel pharmacological approaches for direct targeting of transcription factor dynamics.

Dr. Julie Lessard will discuss the foundational role of chromatin regulatory complexes in shaping the transcriptional landscape in normal and malignant myelopoiesis with an emphasis on the SWI/SNF family of genes in the maintenance, proliferation and differentiation of normal and leukemic hematopoietic stem cells.

Chair:

Olga A Guryanova, MD, PhD
University of Florida
Gainesville, FL, United States

Speakers:

Bruno Di Stefano, PhD
Baylor College of Medicine
Houston, TX, United States
RNA Condensates in Leukemia and Hematopoietic Stress

Ulrich Steidl
Albert Einstein College of Medicine
Bronx, NY, United States
Understanding and Targeting Transcriptional Noise in Normal and Malignant Hematopoiesis

Julie Lessard, PhD
Institute For Research In Immunology and Cancer
Montreal, QC, Canada
Chromatin Remodeling in Normal and Malignant Myelopoiesis

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New Frontiers in Neutrophil Biology

Scientific Committee on Immunology and Host Defense

Saturday, December 6, 2025, 4:00 p.m. - 5:15 p.m. OCCC - W311EFGH

Neutrophils are the most abundant of the white blood cells. This session will explore the rapidly evolving understanding of neutrophils as dynamic, heterogeneous, and immunologically influential cells. Together, all three featured talks will underscore the complexity of neutrophil biology and its relevance to cancer, aging, and immune-mediated diseases, offering new insights and potential targets for therapy.

Dr. Renato Ostuni will highlight how single-cell technologies have revolutionized our view of neutrophil ontogeny. His work reveals that neutrophils are not a uniform population but exhibit remarkable plasticity, adapting to diverse tissue environments. Using data from both mouse models and human samples, he emphasizes the spatial and molecular heterogeneity of neutrophils, particularly within tumor microenvironments such as pancreatic cancer.

Dr. Dominique Bonnet will delve into the impact of clonal hematopoiesis (CH)-associated mutations on neutrophil function. Focusing on TET2 mutations, she will demonstrate how these somatic alterations—common in aging individuals—reshape neutrophil development and impair their antimicrobial capabilities. Using CRISPR-engineered human hematopoietic stem cells transplanted into mice, the work shows that TET2-mutant neutrophils exhibit altered chromatin structure, reduced phagocytosis, and produce compact, less effective neutrophil extracellular traps (NETs). These findings link CH to increased susceptibility to infections and chronic inflammatory diseases such as atherosclerosis and chronic obstructive pulmonary disease.

Dr. Emily Findlay will address the emerging role of neutrophils in modulating adaptive immunity and their contribution to autoimmune and autoinflammatory diseases. Neutrophil presence in lymph nodes and tissues correlates with disease severity in conditions like Crohn’s disease and multiple sclerosis. Dr. Findlay will present evidence that neutrophils influence T cell survival, activation, and exhaustion through direct interactions and NET-mediated signaling. The talk also explores how neutrophils may act as antigen-presenting cells and outlines new preclinical models to study these interactions, with implications for therapeutic intervention.

Chair:

Katherine King, MD, PhD
Baylor College of Medicine
Houston, TX, United States

Speakers:

Renato Ostuni
San Raffaele Scientific Institute
Milan, N/A, Italy
Single Cell Insights Into Neutrophil Ontogeny

Dominique Bonnet, PhD
The Francis Crick Institute
London, ENG, United Kingdom
Effect on Clonal Hematopoiesis Associated Mutations on Neutrophil Function

Emily Gwyer Findlay
University of Edinburgh
Edinburgh, SCO, United Kingdom
Neutrophils in Tumor Immunity

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Strategies To Improve Outcomes After Hematopoietic Cell Transplantation and Adoptive Cell Therapy

Scientific Committee on Transplant Biology and Cellular Therapies

Saturday, December 6, 2025, 9:30 a.m. - 10: 45 a.m. OCCC - W331

This session will provide an overview of recent advances in both hematopoietic stem cell transplantation and adoptive cellular therapies. The audience is expected to learn about important scientific advances in graft manipulation, including in the application of hematopoietic stem transplantation for nonmalignant indications, as well as a timely scientific update on novel strategies to prevent graft-versus-host-disease and recent advances in the fast-evolving field of detecting and treating cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapies.

Chair:

Craig Byersdorfer, MD, PhD
University of Minnesota
Minneapolis, MN, United States

Speakers:

Marie Bleakley, PhD, MBBS, MMSc
Fred Hutchinson Cancer Rsch. Ctr.
Seattle, WA, United States
Novel Graft Manipulation Strategies - From Bench to Bedside

Leslie Kean, MD, PhD
Boston Children's Hospital
Boston, MA, United States
New Preclinical and Translational Approaches to Prevent GVHD

Kai Rejeski, MD
LMU University Hospital
Munich, Bavaria, Germany
Ways to Predict and/or Minimize Hematotoxicity, Infections and Non-Relapse Mortality After Immunotherapy

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The Critical Role of Metabolism in Megakaryocyte and Platelet Biology

Scientific Committee on Megakaryocytes and Platelets

Monday, December 8, 2025, 2:45 p.m. - 4:15 p.m. OCCC - W314

Metabolism is critical in regulating cellular function across a wide range of biological processes. However, much remains unknown about how metabolic pathways influence their development and function in the context of megakaryocytes and platelets. Emerging evidence suggests that platelet function can be significantly affected by metabolic changes, which can also impair the process of thrombopoiesis. Recent publications have highlighted the importance of studying the metabolic regulation in these cells, opening new avenues for understanding how metabolism may impact platelet production and function, as well as its implications in disease states. This is a novel topic in the megakaryocyte and platelet field. The session will span basic and translational research addressing how mitochondria morphology, lipid metabolism, and altered metabolism impact platelet activation, production, and possibly platelet disorders. 

Chair:

Alessandra Balduini, MD
Tufts University
Medford, MA, United States

Speakers:

Jesse Rowley, PhD
UNIVERSITY OF UTAH HEALTH
Salt Lake City, UT, United States
Mitochondria Morphology, Function and Platelet Activation Responses

Koji Eto, MD
Center for iPS Cell Research and Application, Kyoto University
Kyoto, KYO, Japan
Lipid Metabolism, Megakaryocyte Function and Platelet Production

Kathleen Freson, PhD
Katholieke Universiteit Leuven, Department of Cardiovascular Sciences
Leuven, -, Belgium
Altered Metabolisms and Platelet Disorders

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Thromboinflammation

Scientific Committee on Thrombosis and Vascular Biology

Saturday, December 6, 2025, 4:00 p.m. - 5:15 p.m. OCCC - W314

In the 1st century, Celsus described rubor, calor, and dolor – redness heat and pain - as the three signs of inflammation. In the 18th century Rudolf Virchow described his triad of thrombosis. The past 5 years have brought to the forefront the primordial interactions between thrombosis and inflammation. Consultative hematology is often involved in the management of patients with these complex conditions, answering burning questions. As such, we thought it important to highlight some developments with this hot focus. We have asked each speaker to also introduce the link between thrombosis and inflammation in their talk.

Dr. Sonata Jodele will explore the evolving role of the complement system dysregulation in transplant-associated thrombotic microangiopathy (TA-TMA), using it as a model of complement-mediated endothelial injury in the setting of hematopoietic stem cell transplantation (HSCT). Emphasis will be placed on practical strategies for assessing complement activation in clinical settings, including the use of biomarkers like sC5b-9 to support diagnosis and guide therapy. Although complement inhibitors such as eculizumab are not currently approved for TA-TMA, emerging data suggest potential benefit in select high-risk cases. She will also highlight the complex interplay between complement and other inflammatory drivers that may "fuel the fire" in TA-TMA pathophysiology and conclude with a future perspective on integrating multi-omics technologies to inform precision-targeted interventions for complement-driven vascular injury in HSCT.

Dr. Markus Sperandio will present recent work from our group describing a rapid E-selectin-mediated activation process leading to NLRP3 inflammasome activation and subsequent Gasdermin D pore formation, which allows the release of the alarmin and TLR4 ligand S100A8/A9 from neutrophils. Intriguingly, this process is self-limiting with removal of the formed Gasdermin D pores within minutes after E-selectin stimulation through activation of the ESCRT-III machinery.

Dr. Luisa Iruela-Arispe, will explore how mechanical cues intersect with inflammatory pathways to determine endothelial fate, from adaptive remodeling to maladaptive “burning” states that fuel vascular pathology. Endothelial cells are the first responders to hemodynamic forces, continuously translating shear stress into biochemical and transcriptional signals that govern vascular tone, permeability, and inflammation. Specifically, she will discuss how endothelial chemo-mechanical coupling orchestrates vascular homeostasis and how its disruption under disturbed flow initiates chronic inflammation, endothelial dysfunction, and atherogenesis and beyond.

Chair:

Peter L. Gross, MD
University Health Network and Princess Margaret Cancer Centre, University of Toronto
Toronto, ON, Canada

Speakers:

Sonata Jodele, MD
Cinncinati Children's
Cincinnati, OH, United States
Complement On Fire

Markus Sperandio
Ludwig-maximilians-University
Planegg-Martinsried, Germany
The Inflammasone: E-selection-Driven Activation

Luisa Iruela-Arispe, PhD
Northwestern Feinberg School of Medicine
Chicago, IL, United States
Endothelial Chemo-Mechanical Signaling in Response to Shear Stress

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Tracing Bloodlines: Decoding Embryonic Waves of Blood Cell Production and Their Contribution to Disease

Scientific Committee on Stem Cells and Regenerative Medicine

Saturday, December 6, 2025, 4:00 p.m. - 5:15 p.m. OCCC - W312

Recent advances in genetic lineage tracing, barcoding, and single cell technologies have changed our understanding of hematopoietic ontogeny. Rather than the classic view of three waves of primitive and definitive blood production, we now recognize many overlapping waves of blood production that generate an array of hematopoietic populations, many of which persist long into adulthood to shape the blood system and bone marrow niche. Evidence is also emerging that the hierarchy of stem and progenitor cells emerges not in a linear path from stem cell to progenitor, but rather as a multitude of stem and progenitor cells emerging simultaneously in overlapping waves from a diverse hemogenic endothelium. The gradual exhaustion of some of these populations over time may contribute to aging-related blood phenotypes. Further, we now appreciate that many blood populations undergo a fetal to adult identity transition and play key roles in shaping the developing blood system, its supportive niche and hematologic disease. Here, we review these recent findings.

Dr. Momoko Yoshimoto will present about the multiple waves of hematopoiesis occurring in the mouse embryo. Lineage tracing mouse models reveal waves of hematopoietic stem cell (HSC)-independent lymphoid cell contributing to adult immunity. She will also discuss the unique role of fetal-derived B-1 cells in regulating macrophage polarization to prevent CHIP-associated atherosclerosis.

Dr. Claudia Waskow will present about how embryo-derived macrophages actively shape the bone marrow niche, making it amenable to HSCs and providing the foundational architecture needed for lifelong blood formation. Lineage-tracing studies and interventional models establish that this embryonic hematopoietic process is a critical, complementary component of adult blood formation, and necessary for the adult organism's normal immune function.

Dr. Elvin Wagenblast will discuss emerging evidence that some hematologic malignancies originate during fetal hematopoiesis. Distinct fetal-specific genetic and developmental pathways that predispose cells to leukemogenesis and influencing disease initiation and progression have been illuminated, as has the distinct susceptibility of fetal-derived blood cells to oncogenic mutations relative to adult counterparts. Dr. Wagenblast will highlight novel mechanisms through which developmental origin shapes leukemia and therapeutic vulnerabilities, providing potential avenues for targeted intervention in hematologic disorders with fetal origins.

Chair:

Shannon McKinney-Freeman, PhD
St. Jude Children's Research Hospital
Memphis, TN, United States

Speakers:

Momoko Yoshimoto, MD, PhD
Western Michigan University Homer Stryker MD School of Medicine
Kalamazoo, MI, United States
New Insights Into the Dynamics and Heterogeneity of Waves of Blood Production During Development

Claudia Waskow, PhD
Leibniz Institute on Aging, Germany
Jena, Germany
Highlighting the Role of Fetal Blood Cells In Shaping the Life-Long Blood System

Elvin Wagenblast, PhD
Icahn School of Medicine/Mount Sinai
New York, NY, United States
Recent Insights Into the Pathophysiology of Hematologic Disease With Fetal Origins

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TRIMming the Immune Response: Cutting-Edge Insights into Transfusion-Related Immunomodulation

Scientific Committee on Transfusion Medicine

Monday, December 8, 2025, 10: 30 a.m. - 11: 45 a.m. OCCC - W314

Transfusions remain a life-saving treatment, however they can elicit a complex host immune response, characterized by a combination of proinflammatory and/or immunosuppressive outcomes. These responses, also termed transfusion-related immunomodulation (TRIM), are shaped by molecular characteristics of the transfused product and intrinsic cellular signaling pathways within the recipient’s immune cells, which govern how they perceive and react to transfused components. The session will discuss recent insights into the immunomodulatory properties of transfused products and how the recipient’s pre-existing immune state can regulate the outcome of the immune response.

Dr. Benoit Vingert will discuss how extracellular vesicles also known as microparticles (MPs), derived from the budding of plasma cell membranes, may be involved in TRIM syndrome with significant consequences in altering immune functions. This discussion will explore the heterogeneity of microparticles (MPs)—in terms of both quantity and phenotype—including their expression of diverse immunoregulatory surface molecules and their content of immunoactive elements, which can modulate the transfusion recipient’s immune response by either amplifying or suppressing it.

Dr. Nilam Mangalmurti will present recent advances in the field of red blood cell (RBC) immunobiology, highlighting a newly recognized role for RBCs in sensing and regulating nucleic acids in circulation, with functional consequences for innate immune activation, nucleic acid clearance, and vascular homeostasis. The talk will consider implications for transfusion medicine, including how donor RBC immune function may impact recipient inflammation.

Dr. Karina Yazdanbakhsh will discuss the impact of patients underlying pathophysiology with a focus on the role of hemolysis, a characteristic feature of sickle cell disease (SCD). Heme pathways governing monocyte differentiation and their consequential impact on shaping protective versus pathological outcomes in SCD will be highlighted. Therapeutic strategies for targeting these pathways that can potentially mitigate the pathologic effects during transfusions will also be discussed.

Chair:

France Pirenne, MD, PhD
University Paris-Est Créteil
Creteil, France

Speakers:

Benoit Vingert, PhD
INSERM U955
Creteil, France
Little Secrets: Microparticles in Blood Products as Immune Modulators

Nilam Mangalmurti, MD
Perelman School of Medicine
Philadelphia, PA, United States
Donor Alert: Immunomodulatory Roles of Red Blood Cells

Karina Yazdanbakhsh, PhD
New York Blood Center
New York, NY, United States
Special Effects: Recipient Innate Immunity and Transfusion Immunomodulation