Program Co-Chairs:

Sant-Rayn Pasricha, MD,PhD, Walter and Eliza Hall Institute of Medical Research
Fitzroy North, VIC, Australia

Jennifer Trowbridge, PhD,
Bar Harbor, ME

Crosstalk Between Iron Homeostasis and Metabolism

Monday, December 9, 2024, 4:30 p.m. - 5:45 p.m. San Diego Convention Center, Room 29

This session was developed by the Scientific Committee on Iron and Heme.

Maintaining iron balance is fundamental to preserve metabolic functions and energy requirements. This session reflects the current understanding of the reciprocal relationship existing between iron homeostasis and energetic metabolism. It aims to highlight the regulatory role of heme and iron on glucose and lipid metabolism as well as the impact of metabolism on the modulation of the iron status. Novel findings will be presented about the physiologic and pathologic implications of iron-mediated regulation of metabolism, and metabolite-driven control of iron and heme homeostasis. The session will focus on b-thalassemia, sickle cell disease and obesity, and will have broad relevance to all hematologic and non-hematological diseases.

Dr. Antonella Nai will discuss the role of Transferrin Receptor2 (TFR2) in the reciprocal regulation between iron homeostasis, erythropoiesis, and glucose metabolism. TFR2 is an iron sensor acting as a brake of erythropoietin signaling in erythroid cells. Its genetic inactivation in the hematopoietic compartment enhances erythropoiesis and improves anemia in ß-thalassemia. She will present unpublished data demonstrating that Tfr2 deficiency increases the metabolic activity of erythroid cells, thus promoting glucose consumption and reducing blood glycemia. This is particularly relevant in ß-thalassemia, whereby glucose intolerance and diabetes are common and invalidating complications.

Dr. Wei Ying will focus on the connection between iron homeostasis and lipid metabolism. He will present findings related to the role of iron homeostasis in regulating hepatocyte lipogenesis and neighboring cell responses, including hepatic stellate cells, and describe how alterations of these mechanisms drive non-alcoholic fatty liver disease, steatohepatitis and obesity.

Dr. Leitinger will share how heme triggers a unique bioenergetic switch in macrophages, characterized by a metabolic shift from oxidative phosphorylation towards glucose consumption, and its critical role in the effective clearance and detoxification of heme in sickle cell disease. Based on the previous identification of the phosphofructokinase PFKFB3 as key mediator of the metabolic switching in heme-detoxifying macrophages, he will present data about a potential therapeutic strategy involving the inhibition of PFKFB3 in a mouse model of sickle cell disease. Furthermore, the general clinical relevance of these processes for patients with hemolytic disorders will be discussed.

Chair:

Francesca Vinchi, PhD
New York Blood Center
New York,  NY

Speakers:

Antonella Nai, PhD
IRCCS San Raffaele Scientific Institute
Milan,  Italy
Iron, Erythropoiesis, and Glucose Metabolism

Wei Ying, PhD
University of California San Diego
La Jolla,  CA
Iron and Lipid Metabolism

Norbert Leitinger
University of Virginia
Charlottesville,  VA
Heme and Macrophage Metabolism.

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Host Factors Driving Anti-Leukemia Immunotherapy Outcomes

Saturday, December 7, 2024, 2:00 p.m. - 3:15 p.m. Marriott Marquis San Diego Marina, Pacific Ballroom Salons 18-19

This session was developed by the Scientific Committee on Immunology and Host Defense.

This session will cover how the immune microenvironment of the host interacts with leukemia cells and how the donor immune system can exert graft-versus-leukemia (GVL) effects. The speakers will focus on the characterization of immune effector cells and leukemia cells using high resolution RNA and protein analysis, the characterization of metabolites that impact the GVL effect and kinase inhibition strategies to overcome immune escape mechanisms of leukemia cells.

Dr. Catherine Wu will discuss the components critical to devising effective immunotherapy for the treatment of myeloid leukemia, namely the identification of myeloid malignancy antigen targets, and the detection of critical immune cell effectors. The analysis of GvL responses following allogeneic stem cell transplant for AML/MDS, through single cell transcriptome and spatial analysis of marrow specimens, is a particularly instructive setting from which to detect key antigens and cell subpopulations implicated in anti-leukemia responses. The insights gained from the study of such GVL settings promise to provide a roadmap for devising new immunotherapeutic approaches for myeloid malignancies.

Dr. Takanori Teshima will discuss mechanisms of leukemia relapse after allogeneic hematopoietic stem cell transplantation and novel strategies to prevent relapse by inhibiting immune escape of leukemic cells, restoring immune cell dysfunction, and turning “COLD” into “HOT” immune microenvironment. In addition, novel strategies to separate GVL from GVHD by controlling migration and activation of donor T cells in the vicinity of leukemic cells.

Chair:

Robert Zeiser, MD
Universitätsklinikum Freiburg
Freiburg,  Germany

Speakers:

Catherine J. Wu, MD
Harvard Medical School
Boston,  MA
Immune Microenvironment and GVL Effects

Takanori Teshima, MD,PhD
Hokkaido University
Sapporo,  Hokkaido, Japan
Firing Up COLD Tumor Microenvironment to Facilitate GVL

Franziska Blaeschke, MD,PhD
German Cancer Research Center (DKFZ)
Heidelberg,  Germany
Knockin Sequences to Program Durable Cell Therapies Acting Against Leukemia Cells

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Ineffective Erythropoiesis: Insights Into Molecular Mechanisms and Disease Pathophysiology

Saturday, December 7, 2024, 9:30 a.m. - 10: 45 a.m. Manchester Grand Hyatt San Diego, Grand Hall D

This session was developed by the Scientific Committee on Red Cell Biology.

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.

Chair:

Peng Ji, MD,PhD
Northwestern University Medical School
Chicago,  IL

Speakers:

Wassim El Nemer, PhD
French Blood Establishment (EFS)
Marseille,  France
Post-Transcriptional and Signaling Mechanisms in Ineffective Erythropoiesis in Hemoglobinopathies

Elizabeth S. Egan, MD, PhD
Stanford University School of Medicine
Stanford,  CA
Plasmodium Falciparum Influences Erythropoiesis

Sergei Doulatov, PhD
University of Washington School of Medicine
Seattle,  WA
Ineffective Erythropoiesis in Myeloid Neoplasms

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JOINT SESSION: Emerging Therapeutic Strategies Targeting Epigenetic, Transcriptomic, and Metabolic Mechanisms

Sunday, December 8, 2024, 9:30 a.m. - 11: 05 a.m. San Diego Convention Center, Room 24

This session was developed by the Scientific Committee on Epigenetics and Genomics + Scientific Committee on Myeloid Neoplasia.

Recent developments in therapeutic targeting of various mechanisms of epigenetic, transcriptomic, and metabolic vulnerabilities in cancer utilize novel technologies and may provide future breakthroughs. Given the extensive amount of knowledge derived from high throughput methodologies in the last decade, rational targeting is now possible, with sophisticated mechanistic studies to study the effects of targeting. This session will focus on novel research aimed at identifying and targeting these molecules, including novel targeting approaches such as heterobifunctional molecules and others.

Dr. Crabtree will discuss a new approach to make cancer therapeutics by rewiring cancer drivers to activate po pathways of apoptosis) (Gourisankar et al., Nature 2023, PMID: 37495688 ; Sarott et al., Science 2024, PMID: 39361741).  The approach uses chemically induced proximity (CIP) and to kill the cancer cell with its driver. The molecules, called TCIPs (Transcriptional/Epigenetic Chemical Inducers of Proximity) rapidly reverse epigenetic repression of cell death genes and eliminates lymphoma in several CDX and PDX mouse models.

Dr. Cravatt will discuss novel small molecules that target RNA binding proteins.  Traditionally considered undruggable, RNA binding proteins may be targetable through the use of chemo proteomic approaches to identify ligandable sites.  Dr. Cravatt’s group has successfully employed this strategy to develop chemical probes that can engage cysteine residues in RNA binding proteins and regulate their activity in gene regulation.

Dr. Uckelmann will discuss novel inhibitors of transcriptional mechanisms. Previous work of Dr. Uckelmann has focused on elucidating the role of mutant NPM1 (NPM1c) in regulating oncogenic gene expression in acute myeloid leukemia (AML) cells. Her work showed that the chromatin specific function of the NPM1c oncoprotein can be targeted by Menin-MLL inhibitors which are currently in clinical trials for treatment of NPM1c leukemia. In her talk she will discuss emerging developments in our mechanistic understanding and therapeutic targeting of epigenetic regulators in AML.

Dr. Jones will discuss targeting metabolic dependencies in leukemia. Acute myeloid leukemia (AML) cells and leukemia stem cells (LSCs) have unique metabolic properties that can be leveraged to develop new therapeutic strategies. In this presentation, she will discuss complementary approaches to target metabolism in AML and LSCs.  These approaches include mechanisms to target energy metabolism, metabolite regulated protein synthesis and post-translational modifications, as well as the potential for using metabolite abundance to predict resistance to therapy.

Co-Chairs:

Dinesh S. Rao, MD, PhD
University of California Los Angeles
Los Angeles,  CA

Daniel Starczynowski, PhD
Cincinnati Children's Hospital
Cincinnati,  OH

Speakers:

Hannah J Uckelmann, PhD
Frankfurt Cancer Institute
Frankfurt,  Germany
Novel Inhibitors of Transcriptional Mechanisms

Gerald R. Crabtree, MD
Stanford University
Stanford,  CA
Heterobifunctional Molecules Targeting Epigenetic Mechanisms

Benjamin Cravatt, PhD
The Scripps Research Institute
San Diego,  CA
Inhibitors of RNAs and RNA Binding Proteins

Courtney Jones, PhD
Cincinnati Children's Hospital
Cincinnati,  OH
Targeting Metabolic Vulnerabilities

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JOINT SESSION: Molecular Characterization of Lymphomas in Children, Adolescents, and Young Adults

Saturday, December 7, 2024, 4:00 p.m. - 5:35 p.m. Marriott Marquis San Diego Marina, Marriott Grand Ballroom 2-4

This session was developed by the Scientific Committee on Blood Disorders in Childhood + Scientific Committee on Lymphoid Neoplasia.

Dynamic advances in the molecular characterization of lymphomas continue to shape how these malignancies are classified and inform therapeutic targeting. This joint session will provide a state-of-the-science update on next-generation technologies used to explore that special group of lymphoma subtypes that are most prevalent in pediatric, adolescents, and young adults. The speakers represent experts in these methods and will highlight exciting applications in elucidating lymphoma biology (especially age-related differences in pathogenesis), including enhancing clinical management.

Dr. Lisa Roth will discuss ongoing efforts to delineate the genomic landscape of classic Hodgkin lymphoma (cHL). Historically, genetic evaluation of cHL has been limited by the scarcity of Hodgkin and Reed-Sternberg (HRS) cells in cHL tumors. This has been overcome in recent years using fluorescence-activated cell sorting to isolate HRS cells from cHL tissues and evaluation of circulating tumor DNA, which have revealed tumors with high mutational burden, complex structural variants, and genomic subtypes with distinct clinical and molecular characteristics. The applicability of these findings to develop prognostic biomarkers and novel therapeutics will be discussed.

Dr. Tomohiro Aoki will discuss emerging single-cell technologies that have enabled better understanding of the comprehensive interactions within the cHL tumor microenvironment at an unprecedented resolution. Considering current pathogenesis models where HRS cells “recruit and re-educate” their microenvironment to create an immuno-suppressive milieu, cHL has emerged as one of the most exciting fields for application of these cutting-edge technologies. Dr. Aoki will summarize new insights gained using CyTOF, single-cell RNA sequencing and multiplexed imaging techniques, and discuss potential implications for clinical decisions.

Dr. Birgit Burkhardt will provide a comprehensive update of recurrent genetic variants reported in Burkitt lymphoma (BL) in several recent studies. Covering both endemic and sporadic BL, Dr. Burkhardt will highlight the impact of patient age at diagnosis on molecular characteristics and its implications for pathogenesis. Incorporation of specific variants as potential biomarkers for risk group stratification in upcoming BL clinical trials will also be discussed.

Dr. Björn Chapuy will discuss novel (epi)genomic analyses employed to define molecular heterogeneity in B-cell lymphoma subtypes and identify clinically actionable alterations, with a focus on primary mediastinal large B-cell lymphomas (PBMLs). With biometric features that often overlap with cHL, PMBLs are distinguished by their typical manifestation in young female patients and sensitivity to PD-1 blockade. Dr. Chapuy will present evolving approaches to comprehensive genetic analysis used to inform and test response to therapies that target such mechanisms of immune escape.

Co-Chairs:

Nicole Kucine, MD,MS
Weill Cornell Medicine
New York,  NY

Jean L. Koff, MD,MSc
Winship Cancer Institute of Emory University
Atlanta,  GA

Speakers:

Lisa Giulino Roth, MD
Weill Cornell Medicine
New York,  NY
Genomic Landscape in Hodgkin Lymphoma

Tomohiro Aoki, MD, PhD
Princess Margaret Cancer Center
Toronto,  ON, Canada
Sequencing Technologies in Hodgkin Lymphoma

Birgit Burkhardt, MD,PhD
University Hospital Münster
Muenster,  Germany
Age-Related Molecular Changes in Burkitt Lymphoma

Björn Chapuy
Charité - University Medical Center Berlin, Campus Benjamin Franklin
Berlin,  Germany
Functional Genomics of Non-Hodgkin Lymphoma in Children, Adolescents, and Young Adults

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JOINT SESSION: Newly Described Functions in the Vascular Space

Saturday, December 7, 2024, 4:00 p.m. - 5:35 p.m. San Diego Convention Center, Room 25

This session was developed by the Scientific Committee on Megakaryocytes and Platelets + Scientific Committee on Thrombosis & Vascular Biology.

Dysregulated interactions between platelets, immune cells, endothelial cells, and their plasma environment underlie numerous age-related diseases. This joint session will provide an integrated view of the vascular space and will highlight the cellular and molecular mechanisms underlying diseases that primarily afflict the elderly. Specifically, the session will focus on novel discoveries addressing how platelet and endothelial aging may affect neurodegenerative disorders and thrombotic disease, and immune thrombocytopenia (ITP), and will shed light into the role of fibrinolytic factors in shaping the pro-atherogenic plasma lipid profile.

Dr. Nerlov, will discuss how aging affects hematopoietic stem cells (HSCs). He will describe how increased HSC platelet bias due to how age-related increases in TGFbeta signaling is an evolutionarily conserved feature of murine and human hematopoiesis. The role of HSC platelet bias in suppressing lymphoid cell production during aging and how TGFbeta receptor inhibition can increase the ability of aged HSCs to support antiviral immunity will also be discussed.  

Dr. Cooper, will discuss the current understanding of ITP pathogenesis and how the results from novel treatments in ITP may depict different disease types in ITP. ITP is a common bleeding disorder with an increase in incidence after age 60. Understanding the disease phenotype and evolution is needed to improve patient outcomes. However, the diagnosis remains presumptive, and treatment is largely empiric, with many patients rotating through several treatments before having a platelet response.

Dr. Lesniewski will discuss the phenotype of the aging vasculature and the hematopathology underlying mechanisms and potential therapeutic strategies being explored to reverse arterial aging to reduce cardiovascular (CVD) risk in older adults. This is important since several factors contributing to dysfunction of the endothelium (i.e., oxidative stress and inflammation, deregulated nutrient sensing, and cellular senescence) increase with aging and could impact CVD risk.

Dr. Zheng will discuss research demonstrating that hepatocytes are an unappreciated source of tissue-type plasminogen activator (tPA), sense metabolic stresses, and impact the production of tPA and its inhibitor PAI1, thereby influencing the extent of fibrinolysis in obesity. She will introduce findings that tPA binds directly to hepatocyte apoB, preventing it from being loaded with lipids and assembled into lipoproteins. Conversely, tPA's inhibitor, PAI1, has the opposite effect, sequestering free tPA and preventing its interaction with apoB to promote VLDL assembly and increase apoB-lipoprotein cholesterol levels.

 

Co-Chairs:

Lijun Xia, MD, PhD
Oklahoma Medical Research Foundation
Oklahoma City,  OK

Hartmut Weiler, PhD
Versiti Blood Research Institute
Milwaukee,  WI

Speakers:

Claus Nerlov, PhD
University of Oxford
Oxford,  United Kingdom
Platelets and Aging

Nichola Cooper, MD
Imperial College
London,  ENG, United Kingdom
New Insights in MK/PLT Functions and Diseases.

Lisa Lesniewski, PhD
University of Utah Health
Salt Lake City,  UT
Age-Related Endothelial Function

Ze Zheng, MBBS,PhD
Medical College of Wisconsin; Versiti Blood Research Institute
Milwaukee,  WI
Novel Functions of Fibrinolytic Factors in Shaping the Pro-Atherogenic Lipid Profile in Plasma.

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JOINT SESSION: The Fuel & Physiology of Regeneration

Saturday, December 7, 2024, 4:00 p.m. - 5:35 p.m. San Diego Convention Center, Room 24

This session was developed by the Scientific Committee on Hematopoiesis + Scientific Committee on Stem Cells and Regenerative Medicine.

The regulation of hematopoietic stem cell (HSC) regeneration involves a sophisticated interplay between signals from the niche and the nuclear regulatory machinery. Extensive work has been done to identify many key players in both areas. However, conveying the signal to the nucleus is not sufficient without the “doers,” the machineries that execute the cellular processes critical for regeneration. Recent studies have identified several vulnerable processes in HSC physiology, such as proteostasis and energy metabolism, which become imbalanced during HSC exhaustion or dysfunction, i.e., processes involved in HSC culture expansion or aging. This session will closely examine the critical physiological processes and their interplay with other regulatory cues, including nutrient-derived signals (minerals and vitamins) crucial for maintaining healthy regeneration without malignant transformation.

Dr. Robert Signer, will discuss how protein homeostasis has emerged as fundamentally and preferentially important in HSCs. He will review how the protein homeostasis network is uniquely configured to promote hematopoietic stem cell self-renewal. Dr. Signer will further discuss how mechanisms of translational control, protein folding, and protein degradation are rewired throughout life to preserve stem cell fitness and will evaluate consequences of protein homeostasis disruption.

Dr. Marie-Dominique Filippi, will discuss the role of metabolism in HSC functions and how HSCs are highly responsive to changes in metabolite availability. New mechanisms will be presented on how HSC metabolic needs are remodeled during regenerative conditions. Additionally, Dr. Filippi will discuss the usage of branch chain amino acids as a new cell-autonomous metabolic checkpoint that influences HSC replicative lifespan.

Dr. Nina Cabezas-Wallscheid, will discuss how mouse and human HSCs and multipotent progenitors are metabolically regulated from intrinsic to dietary-derived metabolites. Through her work using integrated low-input multi-layer omics data, she will highlight research demonstrating distinct metabolic and epigenetic hubs that are essential in HSCs (and not for their downstream progenitors)

Dr. Britta Will, will discuss integrating nutrients into HSC regulation and iron homeostasis in HSCs. Her lab has uncovered a key role of the readily accessible intracellular labile iron pool in instructing HSC self-renewal. More recently, she has focused on identifying the molecular mechanisms of action, particularly focusing on metabolic and non-enzymatic pathways that rely on iron.

Co-Chairs:

Hanna Mikkola, MD,PhD
University of California, Los Angeles
Los Angeles,  CA

Keisuke Ito, MD, PhD
Albert Einstein College of Medicine
Bronx,  NY

Speakers:

Robert Signer, PhD
University of California San Diego
La Jolla,  CA
Proteomic Health in Hematopoietic Stem Cells

Marie-Dominique Filippi, PhD
Cincinnati Children's Hospital Research Foundation
Cincinnati,  OH
Energy Management in Hematopoietic Stem Cells

Nina Cabezas-Wallscheid
ETH Zürich
Zürich,  Switzerland
Integrating Nutrients to Hematopoietic Stem Cell Regulation

Britta Will, PhD
Albert Einstein College of Medicine
Bronx,  NY
Iron Homeostasis in Hematopoietic Stem Cells.

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JOINT SESSION: Therapeutic Gene Editing of Stem Cells in Classical and Malignant Hematology

Sunday, December 8, 2024, 9:30 a.m. - 11: 05 a.m. San Diego Convention Center, Room 29

This session was developed by the Scientific Committee on Bone Marrow Failure + Scientific Committee on Transplantation Biology & Cellular Therapies.

Gene editing is a novel technology to change specific nucleotides or knockouts in cells, and these are starting to be used clinically. This joint-scientific committee session will include 4 talks that span from basic science to clinical use of gene-edited stem cell products and CAR-T products in malignant and classical hematology.

Dr. Justin Eyquem will discuss his latest work using novel gene editing technologies to improve CAR T-cell function and facilitate their manufacturing. He will present new gene edits associated with improved CAR T-cell functional persistence and novel types of vectors for the generation of CAR T cell in vivo.

Dr. Paulo Rio will present the latest results in optimizing novel genome editing tools, including prime editing, to correct hematopoietic stem cells (HSCs) from Fanconi Anemia (FA) patients. She will discuss the latest advances from her lab in optimizing prime editing technology to efficiently target long-term repopulating HSCs and correct the most common FA mutations in both cell lines and primary HSCs from FA patients.

Dr. Pietro Genovese will present the innovative “epitope editing” strategy for overcoming on-target/off-tumor toxicities in acute myeloid leukemia (AML) immunotherapy. Epitope mapping and library screenings have identified specific amino acid changes that have avoided antibody binding. These have now been introduced into HSPCs via base-editing techniques. Epitope-edited HSPC’s were resistant to CAR-T cell therapy, and enabled specific eradication of patient-derived AML xenografts. Dr. Genovese will discuss the potential of precision immunotherapy for relapsed/refractory AML, non-genotoxic conditioning approaches, and advances in multiplex engineering of HSPCs.

Dr. Julia Skokowa will review recent efforts to establish clinical genome editing to correct severe congenital neutropenia-associated mutations as well as gene editing efforts to inhibit mutated genes in patients' HSCs that may be applicable to other bone marrow failure syndromes. She will also discuss key considerations that are particularly important for gene therapy of pre-leukemic bone marrow syndromes, where gene editing of HSCs should be extremely safe so as not to potentiate the leukemogenic transformation of hematopoiesis. Finally, Dr. Skokowa will present her thoughts on the ethics of gene editing for pre-leukemic bone marrow failure.

Co-Chairs:

Marcela V Maus, MD, PhD
Harvard University/Massachusetts General Hospital
Boston,  MA

Hannah Tamary, MD
Sheba Medical Center, Tel Aviv University
Ramat Gan,  Israel

Speakers:

Justin Eyquem, PhD
University of California San Francisco
San Fransisco,  CA
New Gene Editing Technologies

Paula Rio, PhD
IIS-FJD, UAM
Madrid,  Spain
Gene Editing for Fanconi Anemia Bone Marrow Failure

Pietro Genovese, PhD
Boston Children's Hospital
Boston,  MA
Stem Cell Gene Editing

Julia Skokowa, MD, PhD
University Hospital Tübingen
Tübingen,  Germany
Gene Editing for Severe Congenital Neutropenia – Current Advances and Critical Considerations

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Leveraging Single Cell Multi-Omics to Understand Mechanisms of Myeloid Lineage Expansion in Aging and Disease.

Monday, December 9, 2024, 10: 30 a.m. - 11: 45 a.m. San Diego Convention Center, Room 6DE

This session was developed by the Scientific Committee on Myeloid Biology.

Single cell multi-omic studies of normal and malignant hematopoiesis highlight how hematology remains an ideal testing ground for technologic innovation. Continued advancements in single cell sequencing and the analysis of these complex datasets have informed functional experiments that have enabled the field to improve our understanding of hematopoietic stem cell behavior and myeloid differentiation in response to aging, inflammation, and malignant transformation. This session will showcase innovative transcriptomic and functional genomic studies of the pathways that govern myeloid differentiation in response to aging, inflammation, and malignancy.

Dr. Laurenti will focus on how mutations at the DNMT3A R882 hotspot impact differentiation into mature myeloid cell types in steady-state and inflammatory contexts. She will report evidence implicating neutrophils in an inflammatory vicious circle triggered by the acquisition of DNMT3A R882 mutations in hematopoietic stem cells. She will also discuss findings which could contribute to explain the high risk of leukemia associated with DNMT3A R882 mutations.

Dr. Dick will explore how aging and inflammatory conditions impact myelopoiesis and pre-leukemic clonal expansions. He will focus on the identification of HSC-inflammatory memory (HSC-iM), a new HSC population that remembers prior inflammatory stress and adapts to chronic inflammation through dormancy and impaired differentiation output. He will present evidence that selective advantage of CH-mutant HSCs arise as a consequence of relieving the increased dormancy and decreased differentiation output of HSC-iM. Through scRNA/ATAC analysis, combined with novel lineage trace analysis, evidence will be presented that HSC-iM transmit their activated programs to their myeloid progeny resulting in their pro-inflammatory properties.

Dr. Klein will examine natural variation in human bone marrow biopsies from over 70 individuals with a representation of ages, genders and ethnicities. He will report on the stereotyped covariation identified between certain progenitor and mature cell type frequencies, and present evidence of both constrained and divergent gene expression programs across the 70 individuals. He will also discuss how the tumor microenvironment can impact the function of mature myeloid cells.

Chair:

Esther A. Obeng, MD,PhD
St. Jude Children's Research Hospital
Memphis,  TN

Speakers:

Elisa Laurenti, PhD
University of Cambridge
Cambridge,  ENG, United Kingdom
Hematopoietic Stem Cell Commitment to the Myeloid Lineage

John E. Dick, PhD
Princess Margaret Cancer Centre, University Health Network
Toronto,  ON, CAN
Hematopoietic Stem Cell and Myeloid Progenitor Cell Response to Inflammation

Allon Moshe Klein, PhD
Harvard Medical School
Boston,  MA
Myeloid Progenitor and Mature Neutrophil Responses in Cancer

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Metabolic Deregulation in Hematopoietic Neoplasia: Tumor, The Environment, and Therapies.

Sunday, December 8, 2024, 9:30 a.m. - 10: 45 a.m. Marriott Marquis San Diego Marina, Pacific Ballroom Salons 15-17

This session was developed by the Scientific Committee on Hematopathology and Clinical Laboratory Hematology.

Cellular metabolism and its role in the pathogenesis of hematologic malignancies is an emerging area of research. Recent studies implicate various cellular mechanisms by which oncogenic activation of metabolic pathways contribute to lymphoid and myeloid malignancies as well as their respective tumor environment. In this session, the speakers will discuss the role of deregulated cellular metabolism that contributes to lymphoid and myeloid malignancies and how they may provide novel insights with therapeutic relevance. The metabolic control of T cell differentiation and their function in immunity will also be discussed. This session highlights the opportunities for gaining novel mechanistic insights of hematologic malignancies through global metabolomic studies that has potential to impact the field of T-cell immunology, immunotherapies and facilitate translation to clinical practice.

Chair:

Megan S. S Lim, MD,PhD
Memorial Sloan Kettering Cancer Center
New York City,  NY

Speakers:

Jürgen Maximilian Ruland
Technical University of Munich
Munich,  Germany
Novel Insights in Metabolic Deregulation in Lymphoid Malignancies

Paolo Gallipoli, MD
Queen Mary University of London
London,  United Kingdom
Targeting Metabolic Deregulation in Acute Myeloid Leukemia

Ananda Goldrath, PhD
Allen Institute
Seattle,  WA
Metabolic Control of T Cell Differentiation and Function in Tumor Immunity

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Paradigm Shifts in Hemostasis: From Mechanisms to Therapies and Back

Sunday, December 8, 2024, 4:30 p.m. - 5:45 p.m. San Diego Convention Center, Room 28 A-D

This session was developed by the Scientific Committee on Hemostasis.

Coagulation is not a linear process that ends at clot formation. Rather, coagulation is a network of ever-growing complexity with many mechanisms and pathways for regulation and feedback. The consequences of coagulation extend well beyond clot formation and into processes related to immunity, inflammation, vascular biology and regeneration. This session will highlight three examples for how bi-directional interactions from bench to bedside and back have paved the way to paradigm shifts in mechanistic insights, diagnosis, and treatment options for bleeding disorders and thrombotic complications.

Dr. Annette von Drygalski will discuss the most recent therapeutic paradigms in hemophilia. The continued unraveling of genetic and biochemical mechanisms underlying impaired blood clotting remains critical to inform the development of groundbreaking therapeutic strategies for Hemophilia A and B. Such strategies include extended half-life clotting factor preparations, non-factor-based molecules modifying hemostasis and, lastly, gene therapy. The new therapies have great potential to improve joint bleed prevention and reduce the sequelae of hemophilic arthropathy, which remains one of the most prominent aspects of clinical management in daily practice. Dr. von Drygalski will discuss pathophysiological mechanisms contributing to hemophilic arthropathy, new imaging modalities and joint outcome measures, paving the way for more targeted and individualized treatment strategies.

Dr. Daniël Verhoef will discuss the discovery and (pre)clinical development of a modified [PR1] recombinant form of coagulation factor X, called VMX-C001, which can bypass factor Xa direct oral anticoagulants (DOACs) in patients requiring immediate reversal of anticoagulation. It carries a unique 16 amino acid insertion that was derived from a snake venom factor X that makes VMX-C001 insensitive to inhibition by FXa DOACs. A single intravenous administration of VMX-C001 was shown to restore coagulation assays in animals and human volunteers on FXa-DOACs. VMX-C001 also prevented rivaroxaban induced bleeding in a primate liver injury model. VMX-C001 holds promise as an effective FXa DOAC reversal agent given its favorable half-life, short infusion time, FXa DOAC independent dosing and lack of a prothrombotic effect.

Dr. Cristina Puy will present a comprehensive exploration of coagulation factor XI dynamic interaction with diverse ligands, substrates, and endothelial cell receptors. Delving into the intricate mechanisms, Dr. Puy will elucidate factor XI pivotal role in modulating endothelial cell permeability and barrier function, shedding light on its implications in thrombotic and inflammatory conditions. This presentation will deepen our understanding of factor XI multifaceted involvement in health and disease.

Chair:

Laurent O. Mosnier, PhD
The Scripps Research Institute
La Jolla,  CA

Speakers:

Annette von Drygalski, MD, PharmD, RMSK
University of California San Diego (UCSD)
SAN DIEGO,  CA
Paradigm Shifts in Hemophilia.

Daniël Verhoef, MSc, PhD
VarmX B.V.
Leiden,  Netherlands
Paradigm Shifts in the Reversal of DOACs

Cristina Puy Garcia, PhD
Oregon Health and Science University
Portland,  OR
New Mechanisms That May Fuel the Paradigm Shifts of the Future

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Proteo-Genomics to Better Study Multiple Myeloma Biology and Evolution

Saturday, December 7, 2024, 9:30 a.m. - 10: 45 a.m. Marriott Marquis San Diego Marina, San Diego Ballroom AB

This session was developed by the Scientific Committee on Plasma Cell Neoplasia.

Cancer proteogenomics incorporates methods that integrate mass spectrometry-based measurements of protein abundance and post-translational modifications with genomic, epigenomic and transcriptomic data from preclinical cancer models and patients samples. Such comprehensive multi-omic data provides new biological and diagnostic knowledge that can improve our understanding of malignant transformation and therapeutic outcomes.

This area is new in the field of Plasma Cell Neoplasia and in this session we will discuss how proteogenomic can lead to a better understanding of multiple myeloma (MM) biology and support the development of novel anti-MM therapeutic targets.

Dr. Krönke will discuss the impact of proteogenomic studies on understanding disease progression in plasma cell malignancies. His comprehensive analysis reveals protein-level changes that are not always predictable from genomic or transcriptomic data alone, highlighting the importance of examining protein dynamics in understanding MM pathogenesis. He will further outline how proteogenomic analysis enables the development of new risk stratification models and reveal deregulated proteins and pathways that can be exploited for new therapeutic approaches in MM.

Dr. Maura will discuss how whole genome sequencing can be utilized to reconstruct the genomic landscape and track the temporal evolution of multiple myeloma. These aspects are becoming increasingly relevant, as the timing and mechanisms of plasma cell transformation in the germinal center, along with their progression to MGUS, SMM, and MM, can significantly impact clinical outcomes. He will also explore how comprehensive genomic profiling can identify mechanisms of resistance and predict responses, particularly in the context of immunotherapy using bispecific antibodies and CAR T cells.

Dr. Perna will discuss an integrated pipeline for probing the MM surface proteome (surfaceome) with mass-spectrometry and transcriptomic analyses to identify novel immunotherapeutic targets. She will discuss the contribution that surfaceome makes to MM biology and the pre-clinical development of novel chimeric antigen receptor platforms for MM based on in vitro and in vivo models including patient samples and BCMA-escaped disease. This work may provide a rationale for developing innovative CAR T cells for MM patients.

Chair:

Paola Neri, MD,PhD
Arnie Charbonneau Cancer Institute, University of Calgary
Calgary,  AB, Canada

Speakers:

Jan Kronke, MD
Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health
Berlin,  Germany
Defining the Proteomic Landscape of Multiple Myeloma

Francesco Maura, MD
University of Miami
Palmetto Bay,  FL
Genomic Drivers Involved in Myeloma Progression and Development of Resistance

Fabiana Perna, MD, PhD
H. Lee Moffitt Cancer Center and Research Institute
Tampa,  FL
Proteo-Genomics to Better Study Cell Surfaceome in Multiple Myeloma

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Understanding the Impact of Donor and Recipient Metabolic Variability on Blood Transfusion Outcomes

Saturday, December 7, 2024, 9:30 a.m. - 10: 45 a.m. San Diego Convention Center, Room 7

This session was developed by the Scientific Committee on Transfusion Medicine.

Blood transfusion requires the donation of blood products from a diverse array of individuals with unique genetics and environmental inputs. This results in the quality and overall behavior of the blood products being less standardized and predictable, with direct consequences on transfused recipients. This session will focus on how recently recognized unique genetic and environmental backgrounds of both the blood donor and the transfusion recipient influence the outcomes of patients. Newly applied metabolic tools reveal metabolic variability in donors and recipients, shedding light on fundamental aspects of these differential responses of transfusion in patients, which could guide future strategies for more personalized and effective blood transfusions.

Chair:

Cassandra Dorothy Josephson, MD
Johns Hopkins All Children’s Hospital
St. Petersburg,  FL

Speakers:

Angelo D'Alessandro, PhD
University of Colorado Anschutz Medical Campus
Aurora,  CO
Blood Donor Genetics and Biology Impact Red Blood Cell Transfusion Outcomes

Moritz Stolla, MD
Bloodworks and University of Washington, Pathology and Laboratory Medicine
Seattle,  WA
Unveiling Platelet Metabolism: Implications for Storage and Transfusion

Cheryl Lobo, PhD
Laboratory of Blood-Borne Parasites, Lindsley F. Kimball Research Institute, New York Blood Center
New York,  NY
Impact of RBC Metabolism on the Disease Outcomes of Transfusion Dependent Patients