Scientific Program
The following information is preliminary and subject to change. All times are listed in Central time.
Program Co-Chairs:
Catherine Wu, MD, Dana-farber/Boston Children's Cancer and Blood Disorders Ctr
Boston, MA
David Bodine, PhD, National Institutes of Health
Bethesda, MD
Aplastic Anemia, Dysimmunity and Mutant Clones
Scientific Committee on Bone Marrow Failure
| Saturday, December 10, 2022, 9:30 a.m. - 10:
45 a.m. Ernest N. Morial Convention Center, 288-290 |
Bone marrow failure (BMF) in aplastic anemia (AA) is due to loss of hematopoietic stem cells (HSCs), which in turn, is caused by deranged immunity and inflammation. Somatic mutations in Hla or Piga genes can lead to immune escape, while other clones involving a range of myeloid cancer genes can also emerge, presumably due to a combination of genetic drift and selection. This session will highlight recent cutting-edge research deciphering pathways by which dysimmunity, HSCs defect, and mutant clones can dynamically shape the course of the disease, spontaneously or in response to both immuno-suppressive and eltrombopag therapy.
Dr. Neal Young will show that our understanding of the immune pathophysiology of marrow failure has been deepened by new technologies—single cell ‘omics; new diseases—VEXAS; and new theories—evolutionary biology applied to somatically mutated clones. Sequencing of RNA of single cells combined with time-of-flight cytometry has allowed deep examination of aplastic anemia marrow cells pre- and post-therapy. Somatically mutated hematopoietic targets evade immune attack and survive regenerative stress, and in effector lymphocytes, propagate pathophysiologic immunity. In VEXAS, acquired mutations in a ubiquitylation gene cause hyperinflammatory rheumatologic diseases, and immune activation originates to the hematopoietic stem and progenitor cells. Modern Darwinian principles have yet to be fully applied to “benign” diseases arising in hematopoietic cells and across a wide range of human tissues.
Dr. Daria Babushok will describe the characteristics of clonal hematopoiesis in aplastic anemia, focusing on frequent somatic mutations in Human Leukocyte Antigen (HLA) Class I genes. Dr. Babushok will discuss the genetic mechanisms of HLA Class I loss, and the disproportionate frequency of mutations targeting specific HLA-A and B alleles linked to aplastic anemia pathogenesis. She will review the role and relative pathogenicity of HLA Class I alleles in predisposing to aplastic anemia and will also examine the impact of high pathogenicity alleles on clinical outcomes of aplastic anemia patients.
Dr. Austin Kulasekararaj will describe the current understanding and knowledge about somatic mutations in acquired aplastic anemia. Besides discussing the dynamics of clonal hematopoiesis during the disease course and its impact with both immunosuppressive therapy and eltrombopag, Dr. Kulasekararaj will review the mechanisms of oligoclonal hematopoiesis and their impact on response to treatment. Lastly, He will examine the impact of eltrombopag (both in treatment naïve and relapsed/refractory aplastic anemia) in high-risk clonal evolution and malignant transformation to Myelodysplastic syndrome and Acute Myeloid Leukemia.
Chair:
Jean Soulier, MD, PhD
Hôpital Saint-Louis and University Paris-Cité
Paris,
France
Speakers:
Neal S. Young
, MD
National Institute of Health
Bethesda,
MD
Immune Deregulation in Aplastic Anemia
Daria V. Babushok
, MD
University of Pennsylvania
Philadelphia,
PA
HLA-restricted Attack and Clonal Evolution in Aplastic Anemia
Austin Kulasekararaj
, MD,MBBS,FRCPath,MRCP
King's College Hospital
London,
ENG, United Kingdom
New Biological Insights on Clonal Evolution in the Eltrombopag Era
Childhood Red Cell Disorders: Embracing Technology to Improve How We Manage Challenging Anemias
Scientific Committee on Blood Disorders in Childhood
| Monday, December 12, 2022, 10:
30 a.m. - 11:
45 a.m. Ernest N. Morial Convention Center, 343-345 |
Anemia is the most common hematologic disorder in children worldwide. For many children, anemia is not only a cause of short-term ill-health, it also has a lifelong impact. This session will describe how a range of state-of-the-art technologies are being developed and applied to address challenging questions about the pathogenesis, diagnosis, and management of anemia in children. It will also illustrate how these technologies can be used to deliver practical advances in the management of childhood anemia and show that these benefits can be achieved way beyond the labs where they were first developed including resource-poor settings.
Dr. Deena Iskander will demonstrate the utility of single cell studies in understanding normal human erythropoiesis and its dysregulation in Diamond-Blackfan anemia (DBA). She will describe the clinical heterogeneity of this disease and how single cell RNA sequencing has helped to identify new genotype-phenotype correlations that contribute to disease heterogeneity. Finally, Dr. Iskander will discuss putative mechanisms of erythroid failure revealed by these studies and in turn, potential new therapeutic avenues in DBA.
Dr. Wilbur Lam will discuss new point-of-care and patient-facing technologies to screen for and monitor anemia. He will specifically describe a visual, color-based anemia test that requires a single drop of capillary blood as well as an entirely non-invasive smartphone app that can estimate blood hemoglobin levels with a "fingernail selfie" and how these two complementary technologies can be used synergistically. Dr. Lam will also discuss the accuracy of these technologies and how improvements are being implemented. Lastly, he will discuss the various clinical use cases of these anemia detection technologies for children and adolescents.
Dr. Obiageli Nnodu will describe the strategy and progress in delivering novel therapies in sickle cell disease in Africa. She will focus on advanced therapies that include exchange blood transfusion, hematopoietic stem cell transplantation and Gene Therapy. The strategies she will present highlight the importance of an integrated approach that includes optimizing healthcare, advocacy, research, and training with partnerships at different levels. The goal of this work is to facilitate access of SCD populations in Africa to advanced therapies and participation of healthcare providers, policy makers, educators and researchers from Africa to deliver disease-modifying and curative therapies.
Chair:
Irene Roberts, MD
Weatherall Institute of Molecular Medicine
Oxford,
ENG, United Kingdom
Speakers:
Deena Iskander
, MD, PhD
Imperial College London
London,
ENG, United Kingdom
Dissecting Heterogeneity in Diamond-Blackfan Anemia: Insight from Single Cell Studies and Clinical Findings
Wilbur A Lam
, MD, PhD
Emory University and Georgia Tech Wallace H. Coulter Department of Biomedical Engineering
Decatur,
GA
New Technologies for Assessment of Anemia and Other Hematologic Disorders in Resource Limited Settings
Obiageli E Nnodu
, BMBCH, FWACP (LabMed), FNAMed.
University of Abuja
Abuja,
Nigeria
Managing Severe Sickle Cell Disease- How Can We Deliver Novel Therapies in Resource-Poor Settings?
Emerging Technologies in Hemostasis
Scientific Committee on Hemostasis
| Saturday, December 10, 2022, 9:30 a.m. - 10:
45 a.m. Ernest N. Morial Convention Center, 265-268 |
Emerging technologies are rapidly changing the landscape of diagnosis and therapies in genetic and acquired bleeding disorders. This session will focus on technologies that align with the ASH Research Agenda (including gene editing, vascular biology, and computational analysis in hematology) and features a group of researchers who are at the forefront of developing and/or using these technologies for blood research. Their talks will focus on addressing gene editing of platelets, advanced biomaterials to promote hemostasis in traumatic bleeding, and fluid flow-based diagnostics of von Willebrand factor (VWF) function.
Dr. Christian Kastrup will discuss how platelets fulfill specialized roles in coagulation and hemostasis, their integral role in hemorrhage management, and their potential for diverse applications as cell therapies in the future. Since methods to genetically modify platelets do not currently exist, Dr. Kastrup will expand on the work done in his lab and how him and his team have created an mRNA-based technology to produce exogenous proteins in transfusable platelets, by optimizing lipid nanoparticles, nucleotide modifications, and various RNA elements to promote transfection and translation within donor platelets.
Dr. Ashley Brown will discuss novel engineered biomaterials for promoting hemostasis. She will describe the development and characterization of platelet-like-particles that target fibrin to stop bleeding and promote healing. Dr. Brown will discuss the efficacy, safety, and clearance of these particles in treating bleeding following intravenous injection in small and large animal models of trauma. Lastly, Dr. Brown will also discuss their influence on healing outcomes.
Dr. David Bark will review VWF degradation and the flow mechanisms that drive it. He will discuss microfluidic device designs that can test VWF function in a laboratory environment and how function relates to structure. Lastly, Dr. Bark will examine flow-based point-of-care VWF assessment approaches.
Chair:
Keith B. Neeves, PhD
University of Colorado Denver | Anschutz Medical Campus
Aurora,
CO
Speakers:
Christian J. Kastrup
, PhD
Versiti Blood Research Institute
Milwaukee,
WI
Gene Therapies to Enhance the Hemostatic Function of Platelets
Ashley Brown
, PhD
North Carolina State University and University of North Carolina at Chapel Hill
Raleigh,
NC
Engineered Biomaterials for Hemostasis
David Bark
, PhD
Washington University in St. Louis
Saint Louis,
MO
Microsystems Based Technologies to Measure and Model Hemostasis
Histone Modifications and Chromatin Programs in Clonal Selection and Cancer Emergence
Scientific Committee on Epigenetics and Genomics
| Monday, December 12, 2022, 2:45 p.m. - 4:00 p.m. Ernest N. Morial Convention Center, 275-277 |
Dysregulation of epigenetic processes and chromatin programs are increasingly recognized as hallmarks of cancer and pre-cancerous clonal selection. Epigenetic dysregulation may occur due to ‘non-mutational epigenetic reprogramming’ involving epigenetic alterations independent of specific gene mutations, as well as mutation(s) in epigenetic regulatory genes. While these changes have been well described in normal and malignant hematopoietic processes and disorders, a major challenge in this field has been to functionally demonstrate causal relationships for the development of targeted therapies. This session will highlight recent cutting-edge research defining specific epigenetic and chromatin mechanisms that cause hematopoietic stem cell (HSC) selection, clonal diversification, and progression of hematologic malignancies.
Dr. Gariella Ficz will present on the development and use of epigenetic editing to define causality between aberrant DNA hypermethylation and physiological changes in primary human HSCs and acute myeloid leukemia. Dr. Ficz will discuss implications of these data for our understanding of the biology of aging and pre-cancerous conditions.
Dr. Cristina Pina will present identification of histone acetylation and Polycomb activity as critical elements in stabilizing transcriptional and cellular identity during pre-leukemia progression and leukemia initiation. Dr. Pina will discuss transcriptional noise, noise regulation by histone-modifying complexes, and the role of transcriptional noise in clonal diversification.
Dr. Elisa Oricchio will present identification of histone acetylation as a critical regulator of 3D chromatin structure that is essential for oncogene expression and maintenance of lymphoma. Dr. Oricchio will discuss modulation of 3D chromatin structure by targeting epigenetic modifications to prevent the formation of oncogenic chromatin interactions.
Chair:
Jennifer J J Trowbridge, PhD
The Jackson Laboratory
Bar Harbor,
ME
Speakers:
Gabriella Ficz
, PhD
Cancer Research UK Barts Centre
London,
ENG, United Kingdom
Histone Programs Regulate Human Hematopoietic Stem Cell State
Cristina Pina
, MD
Brunel University London
Uxbridge,
ENG, United Kingdom
Histone Programs Drive Clonal Diversification in Pre-Leukemia
Elisa Oricchio
, PhD
Ecole Polytechnique Federale de Lausanne
Lausanne,
Switzerland
Histone Acetylation as an Driver of Oncogenic Transformation
Iron and Red Cells: A Co-Dependent Relationship
Scientific Committee on Iron and Heme
| Monday, December 12, 2022, 2:45 p.m. - 4:00 p.m. Ernest N. Morial Convention Center, 265-268 |
In the largest organismal iron flow, macrophages recycle iron from senescent erythrocytes for delivery to erythropoietic marrow where iron is incorporated into heme in hemoglobin of new erythrocytes. This session will present recent advances in the study of mechanisms of iron recycling and discuss the profound influence of malaria on the genetic evolution of such mechanisms.
Dr. Shang Ma will describe mechanistic studies that uncovered novel mechanotransduction processes in erythrocyte and recycling macrophages. These processes are disrupted by mutations in the gene Piezo1 that encodes a mechanosensory protein. Hereditary Xerocytosis, caused by mutations in the Piezo1 gene, is a rare disorder in which red blood cells are dehydrated and patients suffer from anemia, splenomegaly, and iron overload. Dr. Ma will discuss how combined human and mouse genetics strategy enables us to understand the role of mechanical forces in health and disease.
Dr. Robin van Bruggen will discuss new insights into the recycling of iron from senescent erythrocytes in the spleen. The novel mechanism determines the entrapment of red blood cells in the spleen through activation of adhesion molecules on erythrocytes, which is followed by hemolysis and the formation of erythrocyte ghosts. Dr. van Bruggen will discuss how these new insights enhance our understanding of conditions in which exaggerated erythrocyte turnover is observed, such as during severe malarial anemia or sickle cell anemia.
Dr. Sarah Atkinson will review the complex relationship between iron, anemia and malaria, and the unique insights into this relationship offered by novel human genetic variants discovered in Africa. As genetic variations in iron homeostasis influence malaria risk, Dr. Atkinson will address how malaria has shaped the evolution of iron homeostasis in Africa.
Chair:
Tomas Ganz, MD,PhD
David Geffen School of Medicine at UCLA
Los Angeles,
CA
Speakers:
Shang Ma
, PhD
The Scripps Research Institute
San Diego,
CA
Piezo1 in Anemia and Iron Overload
Robin Van Bruggen
, PhD
Sanguin
Amsterdam,
Netherlands
Iron Recycling in the Spleen
Sarah H. Atkinson
, MBBS, MRCPCH, PhD
University of Oxford and KEMRI-Wellcome Trust Research Programme
Keppel Street,
United Kingdom
Anemia and Iron Homeostasis in Malaria
JOINT Session - Cell Competition and Clonal Hematopoiesis
Scientific Committee on Hematopoiesis||Scientific Committee on Stem Cells and Regenerative Medicine
| Sunday, December 11, 2022, 9:30 a.m. - 11:
05 a.m. Ernest N. Morial Convention Center, New Orleans Theater AB |
This session will focus on the concept of cell competition, the process by which interactions between cells with different fitness levels within a tissue enables clonal emergence and dominance. It will provide the attendees with a thorough overview of cell competition and how this alters tissue homeostasis in a range of biological models. It will also discuss how cell competition contributes to clonal hematopoiesis in pre-malignant and malignant hematopoiesis. Finally, it will discuss how interactions of hematopoietic stem and progenitor cells with hematopoietic niches are dysregulated to favor clonal hematopoiesis.
Dr. Laura Johnston will introduce the concept of cell competition, providing a brief history of its study in invertebrate and vertebrate genetic models. Dr. Johnston will present an overview of the basic regulatory mechanisms that operate in different contexts of cell competition and super-competition, and discuss how competitive cell-cell interactions affect tissue homeostasis during animal development, in cancer and during aging.
Dr. Alejo Rodriguez-Fraticelli will present results related to the clonal analysis of Dnmt3a-mutant premalignant hematopoiesis. Using conventional and single-cell lineage tracing approaches, Dr. Fraticelli is identifying the functional and transcriptional variation between different mutant Dnmt3a hematopoietic stem cell (HSC) clones. He will also present new evidence regarding the interactions between age-related HSC and Dnmt3a mutations, which clarifies the mechanism that Dnmt3a mutant cells use to compete and expand in detriment of the normal hematopoietic compartment.?
Dr. Ann Mullally will describe the early pathogenesis of myeloproliferative neoplasms (MPN), from acquisition of an MPN phenotypic driver mutation, through the clonal expansion of MPN stem cells, to the development of overt MPN. She will also discuss how recent single-cell approaches have advanced the understanding of the mechanisms underlying clonal dominance and myeloid transformation as it pertains to MPN. Finally, Dr. Mullally will highlight the potential to exploit these new biological insights for therapeutic gain in MPN.
Dr. Dominique Bonnet will discuss how advanced imaging technologies have enabled the study of how cell competition affects interactions with hematopoietic niches. She will describe the clonal dynamics underlying the responses of human hematopoietic stem/progenitor cells (HSPCs) to inflammatory signals in lungs and bone marrow using the immunodeficient mouse xenotransplant repopulating assay. Dr. Dominique Bonnet will also present some preliminary data on the effect of Tet2 mutations in clonal competition with wild-type HSPCs under homeostasis and during inflammation.
Chair:
Louise E. Purton, PhD
St Vincent’s Institute of Medical Research
Fitzroy,
Australia
Fernando D. Camargo, PhD
Harvard University, USA
Boston,
MA
Speakers:
Laura A. Johnston
Columbia University
New York,
NY
Cell Competition and Fitness Concept
Alejo E. Rodriguez-Fraticelli
, PhD
IRB Barcelona
Barcelona,
Spain
HSC Heterogeneity
Ann Mullally
, MD
Brigham and Women's Hospital, Harvard Medical School
Boston,
MA
MPNs as a Paradigm for Clonal Dominance and Myeloid Transformation
Domique Bonnet
, PhD
Francis Crick Institute
London,
ENG, United Kingdom
Cell Competition in the Hematopoietic Niches
JOINT Session - Seed and Soil: The Role of Inflammation in Myeloid Malignancies
Scientific Committee on Myeloid Biology||Scientific Committee on Myeloid Neoplasia
| Saturday, December 10, 2022, 4:00 p.m. - 5:35 p.m. Ernest N. Morial Convention Center, R02-R05 |
Inflammatory signaling is increasingly recognized as a major contributor to human disease, including cancer. The “seed and soil” concept of carcinogenesis underscores our interest in both the cell-intrinsic and cell-extrinsic roles of inflammation in the pathogenesis of myeloid neoplasia. This session will cover dysregulated inflammatory signaling in hematopoietic cells along with the contribution of the microenvironment and will highlight therapeutic implications arising from these newly generated insights.
Dr. Katherine King will discuss evidence that inflammatory signaling contributes to clonal hematopoiesis. She will discuss the current mechanistic understanding of this relationship with a focus on?Dnmt3a?and?Tet2-mutant clones.
Dr. Christina Lo Celso will discuss the contribution of the bone marrow microenvironment to leukemogenesis. Her work has explored the role of extracellular matrix remodeling in regulating Acute Myeloid Leukemia (AML) growth and differentiation, the highly dynamic interactions between AML cells and immune cells, and the impact of infection on the bone marrow microenvironment. Dr. Lo Celso will describe tools developed to capture the complexity of these interactions in the bone marrow microenvironment and discuss our evolving understanding of the dynamics taking place in the bone marrow of healthy humans as they age and as leukemia develops.
Dr. Eric Pietras will discuss the role of dysregulated inflammatory signaling in the pathogenesis of myeloid malignancies. Specifically, his talk will focus on the interplay between inflammation and metabolic dysregulation as potential drivers of selection and expansion of mutant hematopoietic stem and progenitor cells at early stages of myeloid oncogenesis.
Dr. Daniel Starczynowski will describe the role of dysregulated innate immune pathways in pre-leukemic and myelodysplastic syndrome (MDS) hematopoietic cells. He will also discuss the implications of systemic inflammation on the pathogenesis of MDS and on the competitive advantage of MDS cells. Lastly, Dr. Starczynowski will describe emerging therapeutic strategies targeting innate immune and inflammatory pathways in myeloid malignancies.
Chair:
Kimberly Stegmaier, MD
Dana-Farber Cancer Institute
Boston,
MA
Fabiola Traina, MD, PhD
University of Sao Paulo
Ribeirão Preto,
SP, Brazil
Speakers:
Katherine Y. King
, MD, PhD
Baylor College of Medicine
Houston,
TX
Inflammatory Signaling and Clonal Hematopoiesis
Cristina Lo Celso
, PhD
Sir Francis Crick Institute
London,
United Kingdom
Contribution of the Bone Marrow Microenvironment to Leukemogenesis
Eric M Pietras
, PhD
University of Colorado Anschutz Medical Campus
Aurora,
CO
Dysregulated Inflammatory Signaling in the Pathogenesis of Myeloid Malignancies
Daniel T. Starczynowski
, PhD
Cincinnati Children's Hospital
Cincinnati,
OH
Therapeutic Implications of Inflammatory Signaling in Myeloid Malignancies
JOINT Session - The Lymphoma Microenvironment and Its Impact on Therapy
Scientific Committee on Lymphoid Neoplasia||Scientific Committee on Transp Biology & Cellular Therapies
| Sunday, December 11, 2022, 9:30 a.m. - 11:
05 a.m. Ernest N. Morial Convention Center, R02-R05 |
Lymphoma B-cells exist within a complex milieu of immune and stromal cells that play a central role in lymphoma etiology direct cell-cell contact and/or the release of soluble factors. Inter-patient heterogeneity in lymphoma microenvironment characteristics have been linked with divergent outcomes following chemoimmunotherapy and are likely to be major determinants of response or resistance to modern immunotherapeutic approaches such as cell therapy and T-cell engagers. This session will highlight recent advances in the characterization of the lymphoma microenvironment and its association with therapeutic failure, with a focus on chimeric antigen receptor (CAR) T-cell therapy.
Dr. Maher Gandhi will highlight recent advances in spatial imaging and single cell genomics that have provided new insights into how non-cancerous cells behave and interact within histologically distinct lymphoma subtypes. Lymphoma is a cancer of the immune system, in which malignant lymphoid cells co-exist within a sophisticated microenvironmental niche. Manipulating the environment to provide novel targeted therapeutics remains an unmet need.
Dr. Leandro Cerchietti will describe the distinct phenotypes of cancer associated fibroblasts (CAFs) in patients with B- and T-cell lymphomas. He will describe how these populations that include inflammatory and myofibroblastic CAFs are transcriptionally and epigenetically reprogrammed into cancer supporting entities. He will also describe the roles of CAFs throughout the course of disease, their unique role in older lymphoma patients, and potential therapeutic vulnerabilities that can be targeted for lymphoma immunotherapy.
Dr. Frederick Locke will discuss how evidence from lymphoma patient samples collected on CAR-T cell clinical trials, and from patients treated with standard of care CAR-T, paint a picture of the lymphoma tumor mechanisms of resistance to CAR-T. He will describe the impact of tumor associated inflammatory signals and suppressive myeloid cells in the tumor microenvironment and periphery. Dr. Locke will also outline how the pretreatment immune contexture impacts efficacy, and the association between lymphoma cell genomic complexity and response to CAR-T therapy.
Dr. Saad Kenderian will describe the impact of different components of the tumor microenvironment on outcomes of cellular immunotherapy for lymphoma. He will discuss how changes in cytokines, inhibitory myeloid cells, cancer associated fibroblasts, and extracellular vesicles interact with CAR-T cells and induce both toxicity and resistance to therapy. Lastly, he will review current efforts to modulate the tumor microenvironment in order to increase CAR-T cell safety and efficacy.
Chairs:
Michael R. Green, PhD
The University of Texas MD Anderson Cancer Center
Houston,
TX
Kelli MacDonald, PhD
QIMR Berghofer Medical Research Institute
Brisbane,
QLD, Australia
Speakers:
Maher K. Gandhi
, PhD,FRACP,FRCPath
Mater Research, University of Queensland
Brisbane,
QLD, Australia
Ecotypes in Lymphoma
Leandro Cerchietti
, MD
Weill Cornell Medicine
New York,
NY
Stromal Cells in Lymphoma
Frederick L. Locke
, MD
Moffitt Cancer Center
Tampa,
FL
Mapping Effects of the Tumour Microenvironment on CAR T Responses in NHL
Saad S. Kenderian
, MD
Mayo Clinic
Rochester,
MN
Cellular and Cytokine Modulation of the Tumour Microenvironment
JOINT Session: New Tools to Optimize Platelet Transfusion Therapy
Scientific Committee on Megakaryocytes and Platelets||Scientific Committee on Transfusion Medicine
| Saturday, December 10, 2022, 4:00 p.m. - 5:35 p.m. Ernest N. Morial Convention Center, 252-254 |
Historically, the major consideration in platelet transfusion therapy was in obtaining the maximal platelet count. However, recent clinical and basic science studies focusing on both transfused and native platelets have increased our understanding of how to obtain the maximum benefit when transfusing platelets and led us to the conclusion that more isn’t always better. This session will highlight some of these recent advances that have great potential to improve clinical management of platelet transfusion therapy.
Dr. Marie Hollenhorst will describe the glycosylation of platelet glycoprotein Iba (GPIba), which plays important roles in hemostasis, platelet clearance, and the anti-platelet immune response. Dr. Hollenhorst will discuss her comprehensive analysis of GPIba glycosylation, which has resulted in a detailed map of glycosites (amino acid sites of glycosylation) and determination of glycan structures at each glycosite. Physiologic implications of GPIba glycans include ABO blood group (ABH) antigen-containing glycans, sialoglycans, Tn antigen, and T antigen.
Dr. Dianne van der Wal will present the various platelet clearance mechanisms currently described in humans and in animal models. She will discuss the role of GPIb and platelet-attached carbohydrates in physiological clearance and (bleeding) disorders including idiopathic thrombocytopenic purpura. Dr van der Wal will discuss her latest findings on the effect of various donor attributes on the quality of platelet components and implications for platelet clearance and hemostatic efficiency post-transfusion. She will also discuss novel in vitro clearance pathways for platelet microparticles and the potential implications for patients, post-transfusion.
Dr. Martin Schreiber will discuss the effects of leukoreduction and the storage lesion on platelet function in whole blood. He will also discuss the benefits of cold platelet transfusion. Finally, Dr. Schreiber will discuss potential alternative therapies including freeze dried platelets and platelet extracellular vesicles.
Dr. Martha Sola-Visner will discuss the incidence and patterns of bleeding in preterm neonates, and the results from randomized trials of platelet transfusion thresholds in this population. She will then describe the developmental differences that exist between neonates and adults in platelet function and primary hemostasis, and the potential “developmental mismatch” that occurs when adult platelets are transfused into sick neonates. Lastly, she will discuss the effects of platelet transfusions on neonatal hemostasis and inflammation, and the potential mechanisms underlying the increased morbidity and mortality associated with platelet transfusions in this vulnerable population.
Chair:
Maureane Hoffman, MD, PhD
Durham VA Medical Center
Durham,
NC
Kellie Machlus, PhD
Harvard Medical School
Boston,
MA
Speakers:
Marie Alice Hollenhorst
, MD,PhD
Stanford University
Palo Alto,
CA
Glycan Regulation of Immune and Hemostasis Function in Platelet Biology and Transfusion Speakers
Dianne Evertdina van der Wal
, PhD
The Australian Red Cross Lifeblood
Alexandria/Sydney,
Australia
Platelet Clearance by Direct and Indirect Mechanisms: Implications for Platelet Transfusion and Treatment of Different Pathologic Conditions Speakers
Martin Schreiber
, MD
Oregon Health and Science University
Portland,
OR
Platelets in Whole Blood Transfusion, Cold Stored Platelets
Martha Sola-Visner
, MD
Boston Children's Hospital and Harvard Medical School
Boston,
MA
Platelet Transfusion Outcomes in the Preterm Infant – The intersection Between Hemostatic Efficacy and Immune/Inflammatory Modulation of Platelets
Metabolic Regulation and Implications for Red Cells
Scientific Committee on Red Cell Biology
| Monday, December 12, 2022, 4:30 p.m. - 5:45 p.m. Ernest N. Morial Convention Center, 275-277 |
This session will provide an overview of how metabolic control can be regulated in different ways. The speakers will discuss how metabolic regulation can impact normal hematopoiesis and how it can contribute to disease. In addition, the speakers will also discuss how this process can impact the process of red blood cell production of erythropoiesis. This session will provide attendees with a broad perspective on metabolic regulation and also help guide individuals on how metabolism can impact blood cell production in health and disease.
Dr. Navdeep Chandel will discuss?data on how mitochondrial electron transport chain is necessary for hematopoietic stem cell function and transformation by oncogene Notch.??
Dr. Leonard Zon will discuss the control of metabolic pathways in red blood cells by transcription. He will focus on a chromatin factor, TIF1g, that controls coenzyme Q synthesis and the interaction of ferroptosis and metabolism. Dr. Zon will also discuss how stress and reactive oxygen species regulate erythropoiesis.
Dr. Xu will discuss recent findings on metabolic profiles and mechanisms, in particular a glutamine metabolic switch, that function to control normal and ineffective erythropoiesis.
Chair:
Vijay G. Sankaran, MD, PhD
Boston Children's Hospital
Boston,
MA
Speakers:
Navdeep S. Chandel
, PhD
Northwestern University Chicago
Chicago,
IL
Overview of Metabolic Regulation
Leonard I. Zon
, MD
Harvard University
Boston,
MA
Regulation of Metabolism in Hematopoietic Differentiation
Jian Xu
, PhD
University of Texas Southwestern
Dallas,
TX
Regulation of Erythroid Metabolism
Morphology in a Genomic World
Scientific Committee on Hematopathology and Clinical Laboratory Hematology
| Monday, December 12, 2022, 2:45 p.m. - 4:00 p.m. Ernest N. Morial Convention Center, 208-210 |
Rapid advances in Next Generation Sequencing (NGS) have led to a revolution in the genomic analysis of tumors and other pathologic conditions. During the same time there have also been innovations in spatial biology facilitating multiparameter studies that monitor complex protein expression patterns in tissue. NGS genomics data are now being directly combined with spatial analysis to enable the study of single cells and cell types within their tissue context. This session will highlight recent cutting-edge research on the development and application of spatial biology and spatial transcriptomics to tumor biology with a focus on morphology and hematopoietic neoplasms.
Dr. Rong Fan will describe the emerging technologies developed in his laboratory for spatially resolved genome-wide tissue profiling at the cellular level via deterministic barcoding in tissue (DBiT). This omics approach encompasses the spatial mapping of proteins, transcriptome, chromatin accessibility and histone modifications. He will also discuss the application of these technologies to the human lymph node, tonsil, and bone marrow tissues from both healthy donors and patients with hematological malignancies. Spatially resolved multi-omics atlases from these tissues will provide a valuable resource to the field for examining the role of cell-cell interaction and niches in health and disease, and as a potential strategy for therapeutic intervention.
Dr. Peter Sorger will describe the use of highly multiplexed tissue imaging and spatial transcriptomics to study key features of tumor-immune interaction with an emphasis on the invasive margins of solid cancers. The formation of specific immune niches in tumors will be described, as well as the relationships of these niches to the overall organization of spatial tumors. Applications of spatial profiling to bone marrow and liquid tumors will be discussed, as will the impact of highly multiplexed methods on histopathology more generally.
Dr. Simon Haas will describe the application of single-cell and spatially-resolved technologies to gain a holistic understanding of the micro- and macro-anatomy of hematological organs, such as the lymph node. His studies will focus on the spatial evolution of lymphomas and will address the long-standing question of why some lymphomas grow in an organized manner, whereas others grow diffusely- an important topic that has profound clinical implications. Dr. Haas will demonstrate that a reprogramming of the lymph node microenvironment underlies loss of compartmentalization in aggressive lymphomas, illustrating the power of combined single-cell and spatially-resolved technologies for deciphering molecular pathomechanisms.
Chair:
Keith R. Loeb, MD, PhD
Fred Hutchinson Cancer Center
Seattle,
WA
Speakers:
Rong Fan
, PhD
Yale University
New Haven,
CT
Spatial Multi-Omics Profiling of Human Lymphoid and Hematopoietic Tissues
Peter K. Sorger
Harvard Medical School
Boston,
MA
Spatial Landscape of Progression and Immunoediting in Solid Tumors
Simon Haas
, PhD
Max Delbrück Center in the Helmholtz Association
Berlin,
Germany
Combined Single-Cell and Spatially Resolved Mapping of Lymph Node Ecosystems Reveals Fundamental Principles of Lymphoma Tissue Organization
New Therapeutic Targets for Thrombosis That Do Not Cause Bleeding
Scientific Committee on Thrombosis and Vascular Biology
| Sunday, December 11, 2022, 4:30 p.m. - 5:45 p.m. Ernest N. Morial Convention Center, 293-294 |
Since the 1940’s, antithrombotic agents, specifically anticoagulants and antiplatelet drugs, have been successfully used to treat and prevent thrombosis. The impact of these medications cannot be overstated, as these drugs have definitively been shown to reduce the risk and incidence of heart attacks, strokes, and deep venous thrombosis while also enabling life-saving procedures such as dialysis and heart-lung bypass. Unfortunately, a significant adverse effect common to all of these agents is their increased risk of potentially life-threatening bleeding, which can be dose-limiting and even contraindicated in some patients who need these medications the most. However, recent research investigating the intrinsic (contact) pathway of the coagulation cascade as well as groundbreaking work on platelet, leukocyte, and vascular biology are pointing towards the possibilities of new therapeutic targets for thrombosis that do not cause bleeding. This session will bring together key researchers who are pioneering this field to discuss how close we are to achieving this “holy grail” in antithrombotic therapy.
Dr. Helen Phillipou will discuss activated Factor XII (FXIIa) as a target for a next generation anticoagulant and will cover why it is anticipated that inhibition of FXIIa will yield anticoagulant efficacy with minimal risk of inducing bleeding side effects.
Dr. Cristina Puy will describe the current and state-of-the-art knowledge of Factor XI (FXI)’s interaction with various ligands, substrates, and cell receptors that may help develop new therapeutic agents against FXI to prevent thrombosis without causing bleeding.
Dr. Elliot Chaikof will discuss how inhibitors of P-selectin can target thrombosis via novel mechanisms that are not leveraged with traditional antithrombotic therapy and will review the basic and translational science of these novel agents.
Chair:
Wilbur A Lam, MD, PhD
Emory University and Georgia Tech Wallace H. Coulter Department of Biomedical Engineering
Decatur,
GA
Speakers:
Helen Phillipou
, PhD
University of Leeds
Leeds,
ENG, United Kingdom
FXII Inhibition in Prevention of Thrombosis Without Causing Bleeding
Cristina Puy
Oregon Health and Science University
Portland,
OR
FXI Inhibition in Prevention of Thrombosis Without Causing Bleeding
Elliot L. Chaikof
, MD, PhD
Harvard Medical School
Boston,
MA
Inhibition of P-selectin to Target Thrombosis
Overcoming T-cell Burnout and Exhaustion
Scientific Committee on Immunology and Host Defense
| Saturday, December 10, 2022, 2:00 p.m. - 3:15 p.m. Ernest N. Morial Convention Center, 271-273 |
T cell therapeutics encompass a variety of modalities, including Chimeric antigen receptor (CAR)-Ts, engineered- Temperature Coefficient of Resistance (TCRs) and ‘off-the-shelf’ allo-therapies, and have become a central treatment modality for leukemias, lymphomas, and increasingly, for solid tumors. They have revolutionized the field of cancer treatment by providing a living drug, able to expand, seek out its target, and invade the tumor microenvironment, resulting in the ability to treat tumors which were historically impervious to conventional treatment regimens. However, T cell therapeutics also face multiple challenges, many of them intrinsic to the T cell biology that has been harnessed to create these drugs. Amongst the most common, and most significant in driving therapeutic dysfunction, is the entity known as ‘T cell exhaustion’, a complex molecular program in which normal T cells are restrained in order to avoid uncontrolled T cell expansion, cytotoxicity and cytokine release. This process occurs when chronic TCR signaling drives T cells towards a state of hyporesponsiveness, which, in the setting of T cells engineered to fight cancer, can result in loss of anti-tumor functionality. ?This session will highlight state-of-the-art research on mechanisms controlling T cell exhaustion and focus on new strategies to harness and overcome exhaustion in order to engineer optimal T cell therapeutics.?
Dr. Andrea Schietenger will provide insights into CD8 T cell differentiation in the context of cancer and autoimmunity. She will discuss the molecular programs that drive tumor-reactive T cells into dysfunction/exhaustion and how T cells can be reprogrammed for cancer therapy, as well as novel insights into differentiation, function, and heterogeneity of autoimmune T cells.?
Dr. Evan Weber will give an overview of CAR T cell exhaustion biology, highlight recent advancements in overcoming CAR-T cell exhaustion, and propose a conceptual framework to help inform the next generation of anti-exhaustion strategies. He will discuss emerging evidence which suggests that exhaustion can manifest in CAR T cells through chronic CAR signaling, which is associated with poor response in patients.
Dr. Giedre Krenciute will discuss strategies to overcome T cell exhaustion. She will describe how genetic disruption of Dnmt3a, an enzyme that regulates DNA methylation in human CAR T cells, preserves the cell’s developmental potential, proliferative capacity, and effector functions during chronic antigen exposure allowing for a long-lasting antitumor response.
Chair:
Leslie S. Kean, MD, PhD
Boston Children's Hospital
Boston,
MA
Speakers:
Andrea Schietinger
, PhD
Memorial Sloan Kettering Cancer Center
New York,
NY
T-Cell Exhaustion: Molecular Mechanisms in CAR-T and Beyond
Evan Weber
, PhD
Children's Hospital of Philadelphia
Philadelphia,
PA
An Integrated View of T-Cell Exhaustion
Giedre Krenciute
, PhD
St. Jude Children's Research Hospital
Memphis,
TN
CAR-T Cell Dysfunction: Revitalizing the Living Drug
Plasma Cell Dyscrasias: Resistance to Immunotherapy: Mechanisms and Monitoring
Scientific Committee on Plasma Cell Neoplasia
| Monday, December 12, 2022, 10:
30 a.m. - 11:
45 a.m. Ernest N. Morial Convention Center, New Orleans Theater AB |
In the last couple of decades we have witnessed tremendous progress in the therapeutics of multiple myeloma. The advent of proteasome inhibitors, immunomodulatory drugs, CD38 directed monoclonal antibodies and more recently B-Cell Maturation Antigen (BCMA) directed therapies have altered the treatment landscape for the disease. However, the malignant cells in this disease do nearly always ultimately develop resistance to the therapeutic modalities and the disease progresses. Understanding mechanisms of resistance to these therapies is therefore vital to improving patient outcomes.
Dr. Flavia Pichiorri will focus on mechanisms of Daratumumab and BCMA therapy resistance which will include an overview of the literature in the field and published and unpublished data produced in her laboratory.
Dr. Sarah Gooding will discuss the challenges of the development of resistance to immunomodulatory drugs (IMiD®) in the long-term management of patients with myeloma. ?She will discuss the mechanisms by which resistance may arise; this may be due to the selection of drug resistant subclones during therapy exposure, or changes in the bone marrow and immune microenvironment. The Cereblon drug binding protein may be lost due to a range of mechanisms. Dr. Gooding will discuss whether we may be able to move towards better targeting of IMiD drugs by implementing resistance marker tracking into the clinic.
Dr. Jens Lohr will discuss conceptual advantages of cell-free DNA over disease markers that are currently used in clinical routine care, the benefits and limitations of adding cell-free DNA interrogation to the currently available parameters of response, its value for disease assessment and as a tool to refine clinical decision-making. Liquid biopsy approaches with cell-free DNA interrogation are powerful tools to obtain information about multiple myeloma without the need for invasive bone marrow biopsy.
Chair:
Ravi Vij, MD, MBBS
Washington University in St. Louis
St. Louis,
MO
Speakers:
Flavia Pichiorri
, PhD
City of Hope
Duarte,
CA
Resistance to CD38 and BCMA Targeted Therapies
Sarah Gooding
, MD, PhD
University of Oxford
Oxford,
United Kingdom
Resistance to Immunomodulatory Drugs
Jens G. Lohr
, MD, PhD
Dana Farber Cancer Institute
Boston,
MA
Cell Free DNA Analysis