American Society of Hematology

2017 Scientific Program

The Scientific Program will be held Saturday, December 9, and Sunday, December 10, with each session being offered twice. A question-and-answer period will occur at the end of each individual speaker presentation. Invited abstracts of these sessions will be available in the annual meeting app and on the ASH website.

Program Co-Chairs:

Scott Armstrong, MD, PhD, Dana-Faber Cancer Institute
Boston, MA

Andrew Weyrich, PhD, University of Utah
Salt Lake City, UT

Ad Hoc Scientific Committee on Epigenetics and Genomics

Novel Epigenetic Modifications in Cancer and Development

Sessions Offered Twice:
Saturday, December 9, 2017
4:00 p.m. - 5:30 p.m.

Georgia World Congress Center, Bldg B- Lvl 5- Murphy BR 1-2
Sunday, December 10, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg C- Lvl 1- Hall C4
Epigenetic modifications help guide developmental fate decisions in hematopoiesis, and disruption of the epigenome is a common feature in a variety of hematopoietic malignancies. Technological advances have allowed interrogation of the epigenome at an unprecedented resolution. These data present new challenges and opportunities. While we now describe the distribution of these marks in more detail than ever, there is much to be learned about how these epigenetic patterns regulate gene expression and genome organization. Understanding these processes is of critical importance for the development of epigenetic-based therapies in hematopoietic disease.

Dr. Maria Figueroa will address the role of cytosine methylation in normal aging and leukemias. The DNA methylation pathway is regulated through the function of the DNA methyltransferases and the ten-eleven translocation (TET) proteins. These proteins are frequently mutated in both aging-related clonal hematopoiesis of indeterminate significance (CHIP) as well as in myeloid malignancies. In addition, mutations in IDH1/2 can also affect the function of TET proteins. This presentation will explore the normal role of these proteins and how mutations in them interact to impact the epigenetic makeup of normal and malignant cells.

Dr. Anjana Rao will describe the functions of TET family of enzymes, which oxidize the 5th base, 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and further oxidized derivatives. TET proteins are implicated in numerous biological processes, including neuronal and embryonic development, cell lineage specification, and cancer. Loss-of-function mutations in TET2 are frequent in lymphoid and myeloid cancers in humans, and Dr. Rao has shown in mouse models that profound TET loss-of-function resulting from deletion of both the TET2 and TET3 genes is associated with the rapid and fully penetrant development of aggressive lymphoid and myeloid cancers. These studies, and the underlying mechanisms, will be discussed.  

Dr. Frank Lyko will elucidate the molecular mechanisms that link RNA methylation to the regulation of protein synthesis and discuss how these mechanisms contribute to the regulation of hematopietic differentiation. RNA methylation represents a novel expansion of traditional epigenetic concepts. Loss of RNA methyltransferase activity in mouse models results in complex cellular differentiation phenotypes, including in the hematopoietic system.

Chair:

Grant A. Challen, PhD
Washington University School of Medicine
St. Louis, MO

Speakers:

Maria E. Figueroa, MD
University of Miami
Miami, FL
DNA Methylation in Cancer and Development: An Evolving Paradigm

Anjana Rao, PhD
La Jolla Institute for Allergy and Immunology
La Jolla, CA
Beyond Cytosine Methylation: Ten-Eleven Translocation Proteins, Oxidized Methylcytosines, and Cancer

Frank Lyko, PhD
German Cancer Research Center
Heidelberg, Germany
RNA Methylation and Its Role in the Hematopoietic System

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Joint Session: Scientific Committee on Myeloid Biology & Scientific Committee on Myeloid Neoplasia

Clonal Evolution in Myeloid Malignancies

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:30 a.m.

Georgia World Congress Center, Bldg C- Lvl 1- Hall C1
Sunday, December 10, 2017
9:30 a.m. - 11:30 a.m.

Georgia World Congress Center, Bldg C- Lvl 1- Hall C1
Defining the molecular progression from a preleukemic state to overt malignancy is one of the most pressing scientific questions under current investigation. This session will focus on several systems in which the clonal evolution of myeloid malignancies is being defined.

Dr. Christina Curtis will discuss approaches for quantifying the evolutionary dynamics of tumor progression in a patient-specific manner. She will describe how a population genetics framework can be used to quantify the signals of selection embedded in cancer genomes in order to classify distinct modes of tumor evolution. Dr. Curtis will also describe the attendant clinical implications that can forecast tumor progression.

Dr. Timothy Ley will describe his current work on the combinatorial complexity in the acquired genetic mutations found in acute myeloid leukemia (AML) and the application of molecular insights into patients with intermediate-risk AML with unpredictable outcomes. He will address methods to assess subclonal structure, how assessment regarding the clearance of subclones from each patient is being tested in an ongoing clinical trial, and how this work may improve risk prediction.

Dr. Daniel Link will discuss emerging questions concerning the development of clonal hematopoiesis, including what drives expansion of hematopoietic clones, what role external hematopoietic stressors, such as exposure to chemotherapy, play in the development of clonal hematopoiesis, why so few people with clonal hematopoiesis develop a myeloid malignancy, and whether certain mutations confer a higher risk of transformation.

Dr. Anna Brown will discuss clonal evolution in the context of germline hematological malignancy predisposition syndromes as well as the adaptation to stress that may trigger this evolution. She will address whether genetic and/or epigenetic clonal adaptation act to revert antecedent cytopenias and immunodeficiency or whether they constrain expression of the germline mutated allele and alter disease penetrance in carriers. Other clonal evolution triggers, such as infection or stem cell transplantation, that may lead to malignancy onset will also be discussed.

Speakers:

Christina Curtis, PhD
Stanford University School of Medicine
Stanford, CA
Population Genetics Approaches to Quantify Clonal Evolution

Daniel C. Link, MD
Washington University School of Medicine
St. Louis, MO
Clonal Evolution During Stress Hematopoiesis

Anna L. Brown, PhD
SA Pathology and University of South Australia
Adelaide, Australia
Clonal Evolution in the Setting of Germline Predisposition

Timothy J. Ley, MD
Washington University in St. Louis
St. Louis, MO
Clonal Evolution and Relapse in Adult De Novo Acute Myeloid Leukemia

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Scientific Committee on Blood Disorders in Childhood

Primary Immunodeficiencies From Childhood to Adulthood

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg A- Lvl 4- Marcus Aud.
Saturday, December 9, 2017
4:00 p.m. - 5:30 p.m.

Georgia World Congress Center, Bldg A- Lvl 4- Marcus Aud.
Next generation sequencing allows the identification of causative heterozygous mutation for primary immunodeficiency in sporadic cases. In this session, we will hear several examples for genes causing diseases in a heterozygous state. The clinical phenotype of patients can be variable and patients with primary immunodeficiency might not only be diagnosed during childhood but also as young adults or adults because of complications of cancer or autoimmunity.

Dr. Anne Durandy will start this session with a talk focusing on the clinical and immunological phenotypic and genetic heterogeneity of recently molecularly characterized primary antibody deficiencies, among them the activated PI3K delta syndromes and the NFkB-deficiencies.

Dr. Troy Torgerson will present the current therapeutic approaches used to treat disorders associated with dysfunction in the regulatory T cell and will discuss insights gained by characterizing these PIDs into Treg development and function.

Dr. Jennifer Puck will present examples for diagnoses made for infants discovered to have T cell insufficiency by newborn screening. She will explain how variants found by deep sequencing were proven to be disease-causing in in vitro and in vivo studies.

Chair:

Marina Cavazzana, MD, PhD
Hôpital Necker-Enfants Malades
Paris, France

Speakers:

Anne Durandy, MD, PhD
Université Paris Descartes
Paris, FRA
Primary Antibody Deficiencies: Scientific Discoveries Leading to Challenging Paradigms in a Complex Disease Landscape

Troy R. Torgerson, MD PhD
University of Washington and Seattle Children's Hospital
Seattle, WA
Genetic Disorders of Immune Tolerance: The Flip Side of Immune Deficiency Where Autoimmunity Trumps Infection

Jennifer Puck, MD
UCSF School of Medicine
San Francisco, CA
Diagnostic Challenges in the Era of Genomic Sequencing and Newborn Screening

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Scientific Committee on Bone Marrow Failure

Genetic Pathways That Disrupt Hematopoietic Stem Cell Function in Inherited Bone Marrow Failure

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg A- Lvl 4- A411-A412
Saturday, December 9, 2017
2:00 p.m. - 3:30 p.m.

Georgia World Congress Center, Bldg A- Lvl 4- Marcus Aud.
Study of the classic inherited bone marrow failure diseases Fanconi anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome have provided major insights into DNA repair, telomere maintenance, and ribosome biogenesis. This session will focus on recent advances that provide new insights into mechanisms that lead to stem cell failure and leukemogenesis.

Dr. Inderjeet Dokal will discuss recent studies that have led to the identification of the new bone marrow failure disease genes DNAJC21 and ERCC6L2. Functional studies suggest that DNAJC21 is crucial for 60S ribosome maturation (and therefore ribosome biogenesis), and that ERCC6L2 is important in the DNA damage response and mitochondrial function. Collectively, these discoveries bring into focus new biological connections and pathways whose constitutional disruption is associated with defective hematopoiesis.

Dr. Steven Holland will discuss germline haploinsufficiency of GATA2 that leads to several well-recognized immunodeficiency syndromes associated with eventual loss of monocytes, dendritic cells, B and natural killer lymphoid cells. It is also critical for endothelial development and is associated with later-onset lymphedema. GATA2 mutations are also associated with a broad hematological phenotype that includes an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelomonocytic leukemia (CMML), aplastic anemia, or neutropenia. Recent genetic, molecular, and cellular studies show some genotype-phenotype correlations, especially around lymphedema. There are also important effects of specific mutations on penetrance, with intronic mutations carrying lower rates of penetrance. The pathophysiological mechanisms that lead to different aspects of the disease are still emerging. Bone marrow transplantation has been highly effective at arresting the hematologic, virologic, and pulmonary manifestations of the disease, but so far the lymphatic components have not been affected. GATA2 haploinsufficiency remains a complex and protean disease.

Dr. Marc Raaijmakers will discuss emerging insights into hematopoietic cell non-autonomous contributions to bone marrow failure and leukemogenesis. Shwachman-Diamond syndrome, characterized by bone and blood abnormalities, has a striking propensity for leukemic transformation, and its monogenic origin provides a unique model disease to explore this concept. Data from mouse models and human disease will be presented with an emphasis on inflammatory signaling in the hematopoietic stem cell niche and its broader significance to other bone marrow failure and leukemia predisposition syndromes.

Chair:

Colin A. Sieff, MB, BCh
Dana-Farber Cancer Institute, Boston Children's Cancer and Blood Disorders Center
Boston, MA

Speakers:

Inderjeet Dokal, MD
Barts and Queen Mary University London
London, United Kingdom
New Bone Marrow Failure Genes: DNAJC21 and ERCC6L2

Steven M. Holland, MD
National Institute of Allergy and Infectious Diseases, National Institutes of Health
Bethesda, MD
GATA2 in Bone Marrow Failure

Marc Hermanus Gerardus Petrus Raaijmakers, MD, PhD
Erasmus Medical Centre
Rotterdam, Netherlands
Deconstructing Niche Contributions to Bone Marrow Failure and Leukemogenesis in Shwachman-Diamond Syndrome

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Scientific Committee on Hematopathology and Clinical Laboratory Hematology

Next-Generation Sequencing in Routine Diagnostics: Are We There Yet?

Sessions Offered Twice:
Saturday, December 9, 2017
7:30 a.m. - 9:00 a.m.

Georgia World Congress Center, Bldg A- Lvl 4- A411-A412
Sunday, December 10, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg C- Lvl 3- Georgia BR 1-3
Next-generation sequencing (NGS) has been instrumental in broadening our knowledge of the genomic landscape of hematologic malignancies, and their application as diagnostic and prognostic tools has been rapidly expanding. This session will focus on the utility of NGS in the routine hematologic practice. 

Dr. Kojo Elenitoba-Johnson will discuss the factors that can affect the effective implementation of NGS-based testing in the clinical laboratory, with particular focus on hematologic malignancies. This will include understanding the parameters affecting selection of platforms, providing considerations for disease-based panels or broad/exome-wide analyses and for clinical decision support. Dr. Elenitoba-Johnson will also address challenges in setting up large-scale genomic sequencing assays deployed in a variety of laboratory settings.

Dr. Elaine Lyon will discuss the rapid evolution of genomic testing. She will address professional guidelines available to laboratories to establish quality metrics. In addition, Dr. Lyon will address expectations of data quality and elements of reporting identified variants and their interpretation. She will also discuss the molecular community’s efforts to address consistency in using guidelines. 

Dr. Torsten Haferlach will discuss which NGS option (single genes, panels, whole exome sequencing, whole genome sequencing, RNA sequencing) may be ready for real-time precision medicine. The use of whole exome sequencing will be discussed in detail. Important issues that require attention include instruments, assays, coverage, bioinformatic support for data curation, clinically relevant reporting, and advice for treatment decisions, if actionable. All these chain links are mandatory to allow clinical applicability. Dr. Haferlach will address recent advantages in using whole-exome sequencing for clinical decision making and will define and predict steps for the near future.

Chair:

Maria A. Proytcheva, MD
University of Arizona
Tucson, AZ

Speakers:

Kojo S.J. Elenitoba-Johnson, MD
University of Pennsylvania
Philadelphia, PA
NGS-Based Diagnostics in Hematopathology: Strategies for Implementation in a Clinical Environment

Elaine Lyon, PhD
ARUP Laboratories
Salt Lake City, UT
Understanding the Genome: Professional Guidelines in Clinical Genomic Testing and Interpretation

Torsten Haferlach, MD
Munich Leukemia Laboratory GmbH
Munich, Germany
Whole Exome Sequencing in Patients With Hematologic Malignancies: Ready for Real-Time Precision Medicine?

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Scientific Committee on Hematopoiesis

Hematopoietic Stem Cell Generation: Reprogramming and Expansion

Sessions Offered Twice:
Saturday, December 9, 2017
4:00 p.m. - 5:30 p.m.

Georgia World Congress Center, Bldg A- Lvl 4- A411-A412
Sunday, December 10, 2017
7:30 a.m. - 9:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 5- Murphy BR 1-2
Studies of the hematopoietic system have pioneered stem cell research, and hematopoietic stem cell transplantation has provided increasingly effective curative treatments for malignant and non-malignant diseases over many decades. Recent research breakthroughs provide opportunities for continued improvement in stem cell therapies as well as their broader application. Improved strategies for ex vivo generation and expansion of hematopoietic stem and progenitor cells promise to significantly impact transplantation therapy and will likely be necessary for effective application of genome editing to regenerative medicine. This session will focus on recent advances in ex vivo hematopoietic reprogramming and HSC expansion.

Dr. Kateri Moore will address transcription factor-mediated reprogramming of somatic cells to hematopoietic cells. Similarities between the reprogramming process and developmental hematopoiesis will be discussed, and Dr. Moore will present studies showing that the same three transcription factors effective in reprogramming murine cells will also reprogram human fibroblasts into hematopoietic stem and progenitor cells. Gene expression analyses at different time points of reprogramming will also be presented along with chromatin immunoprecipiation-sequencing studies to explore how these transcription factors remodel chromatin and reset the epigenetic landscape to initiate cell fate changes into a hemogenic program.

Dr. Jonas Larsson will discuss the application of RNAi screens and chemical compound to identify modifiers of human hematopoietic stem and progenitor cell self-renewal under ex vivo culture conditions. He will describe two distinct categories of modifiers – epigenetic regulators and culture-induced stress response genes, and discuss strategies to target these factors to enhance the ex vivo propagation of HSCs. Dr. Larsson will also discuss work to define phenotypic markers that can precisely identify HSCs in culture, as well as strategies to more efficiently assay human HSCs in vivo using xenograft models and cellular barcoding.

Dr. Kristin Hope will discuss the engineering of cellular pathways as a means to achieve ex vivo HSC expansion with a particular focus on modulation of the post-transcriptional circuitry. HSC homeostasis is subject to post-transcriptional control by RNA-binding proteins, which work to ensure precise regulation of gene expression by modulating mRNA splicing, polyadenylation, localization, degradation, or translation. Dr. Hope will summarize advances that capitalize on functional approaches and unbiased transcriptome and proteome-scale methods to define the tenets that govern this regulation. She will also summarize key downstream circuitries of HSC-regulating RNA-binding proteins whose targeting could provide the basis for novel regenerative treatments.

Chair:

Warren S. Alexander, PhD
The Walter and Eliza Hall Institute of Medical Research
Parkville, Australia

Speakers:

Kateri A. Moore, DVM
Icahn School of Medicine at Mount Sinai
New York, NY
In Vitro Hematopoietic Reprogramming and Generation of Hematopoietic Stem Cells

Jonas Larsson, MD, PhD
Lund University
Lund, Sweden
RNAi Screens for Maintenance of Hematopoietic Stem Cell Phenotype During Culture

Kristin Hope, PhD
McMaster University
Hamilton, ON, Canada
Enforcing Post-Transcriptional Circuitries to Achieve Human Hematopoietic Stem Cell Expansion

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Scientific Committee on Hemostasis

Impact of the Contact Pathway on Disease States: Molecular Mechanisms

Sessions Offered Twice:
Saturday, December 9, 2017
7:30 a.m. - 9:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 2- B211-B212
Saturday, December 9, 2017
4:00 p.m. - 5:30 p.m.

Georgia World Congress Center, Bldg B- Lvl 3- B304-B305
The contact pathway of coagulation is known to have a dispensable role in hemostasis. It also contributes to thrombosis, inflammation, innate immunity, and other pathological conditions. This session will focus on newly identified entities that modulate contact activation and inflammation in pathophysiologic disease states. Biochemical mechanisms and potential therapeutic interventions will be presented.

Dr. James Morrissey will discuss the cellular sources of polyphosphate and their roles in modulating the blood clotting and complement pathways in hemostasis, thrombosis, and inflammation. Microbial polyphosphate is suspected of having roles in host-pathogen interactions, while polyphosphate released during cell and tissue injury may be one of the damage-associate molecular patterns (DAMPs) contributing to trauma-induced coagulopathy. Dr. Morrissey will discuss polyphosphate as a potential antithrombotic drug target.

Dr. Patricia Liaw will present how mediators such as damage-associated molecular patterns have a crucial role in the pathogenesis of disseminated intravascular coagulation.  Upon cell death and/or cell activation, extracellular DNA and DNA-binding proteins are released into circulation. These molecules influence hemostasis by inducing platelet aggregation, promoting coagulation activation, activating endothelial cells, and inhibiting fibrinolysis. Basic and translational studies will be presented to provide insights into extracellular DNA and DNA-binding proteins as targets for intervention.

Dr. Sidney Strickland will relate how amyloid-ß peptide (Aß) influences central nervous system hemostasis and thrombosis in the pathogenesis of Alzheimer’s disease (AD). Aß, a causative factor in AD, is a contact system activator and inhibits fibrinolysis leading to brain inflammation and persistent fibrin clots, which contribute to the neurodegeneration and cognitive decline observed in AD. In AD mouse models, contact system inhibition and reducing fibrin levels ameliorates AD pathology. These effects of Aß suggest new therapeutic strategies to treat AD as a thrombo-hemorrhagic disorder.

Chair:

Rodney M. Camire, PhD
Children's Hospital of Philadelphia
Philadelphia, PA

Speakers:

James H. Morrissey, PhD
University of Michigan Medical School
Ann Arbor, MI
Poly-P as Modulator of Hemostasis, Thrombosis, and Inflammation

Patricia C. Liaw, PhD
McMaster University Div. of Hematology & Thromboembolism
Hamilton, ON, CAN
Mediators of Disseminated Intravascular Coagulation: Molecular Mechanisms

Sidney Strickland, PhD
The Rockefeller University
New York, NY
Impact of the Coagulation System on the Pathogenesis of Alzheimer's Disease

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Scientific Committee on Immunology and Host Defense

New Approaches to Understanding Microbial Immune System Interactions

Sessions Offered Twice:
Saturday, December 9, 2017
4:00 p.m. - 5:30 p.m.

Georgia World Congress Center, Bldg C- Lvl 1- Hall C4
Sunday, December 10, 2017
7:30 a.m. - 9:00 a.m.

Georgia World Congress Center, Bldg C- Lvl 3- Georgia BR 1-3
The immune system has evolved over millions of years to respond to a vast array of infectious pathogens. However, over the past decade the increasing resistance of bacteria, fungi, and viruses to standard therapies have challenged researchers to better understand how to exploit the innate and adaptive immune response to better treat infectious disease. This session will focus on cutting-edge approaches to better understand current concepts regarding host-pathogen interactions.

Dr. Mark Davis will describe the response of adaptive immune cells at the single cell level to bacterial and viral pathogens.

Dr. Sarah Gaffen will discuss the multifaceted role of IL-17 in immune responses. IL-17 drives pathology in a number of autoimmune conditions, and biologic therapies targeting the IL-17/Th17 pathway have shown impressive success in the clinic. Conversely, IL-17 is a central driver of immunity to infections, particularly those caused by the commensal fungus Candida albicans. In this session, Dr. Gaffen will discuss recent advances in the IL-17 signal transduction pathway, with an emphasis on the role of IL-17 in driving autoimmunity and protecting from mucosal candidiasis.

Dr. Antonio Lanzavecchia will discuss how the analysis of the human antibody response can reveal fundamental mechanisms and provide new tools to fight pathogens. Cell culture-based methods are used to interrogate memory B cell repertoires and to isolate antibodies selected on the basis of their neutralizing potency and breadth. These antibodies are candidates for prophylaxis and therapy of infections and represent useful tools for vaccine design. The genealogical analysis of B cell clones is used to dissect the role of somatic mutations in affinity maturation, diversification, and in the generation of autoantibodies. The systematic analysis of the antibody response to malaria-infected erythrocytes has led to the surprising discovery of a new mechanism of antibody diversification, which relies on templated insertions of genomic DNA sequences into immunoglobulin genes.

Chair:

Jonathan S. Serody, MD
University of North Carolina at Chapel Hill
Chapel Hill, NC

Speakers:

Mark Davis, PhD
Stanford University
Stanford, CA
New Approaches to Human Immunology

Sarah Gaffen, PhD
University of Pittsburgh
Pittsburgh, PA
IL-17-Driven Immune Signaling in Autoimmunity and Fungal Infections

Antonio Lanzavecchia, MD
Institute for Research in Biomedicine
Bellinzona, CHE
Dissecting Human Antibody Responses: Useful, Basic, and Surprising Findings

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Scientific Committee on Iron and Heme

Iron Trafficking: Ins and Outs in Organelles, Organs, and Organisms

Sessions Offered Twice:
Saturday, December 9, 2017
2:00 p.m. - 3:30 p.m.

Georgia World Congress Center, Bldg C- Lvl 2- C211-C213
Sunday, December 10, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 2- B216-B217
Iron plays an essential role in hemoglobin synthesis as well as other critical biological processes such as oxygen transport, ATP generation, and DNA metabolism. Erythroid precursors satisfy their extreme iron requirements through receptor-mediated endocytosis of iron-bound transferrin, which is routed to mitochondria for heme synthesis and Fe-S cluster biogenesis. Other cell types also express molecules dedicated to the transport, utilization, and storage of iron. As a result, disruptions in iron trafficking can result in various forms of anemia and cause pathology in other organs. This session will discuss current knowledge on iron trafficking in erythroid cells, present emerging roles of the transferrin receptor in non-erythroid cells, and summarize recent clinical advances in therapeutic iron supplementation.

Dr. Mark Fleming will provide an overview of iron trafficking in erythroid precursor cells and will describe how forms of congenital sideroblastic anemia result from genetic defects in this process

Dr. Nancy Andrews will discuss the role of iron in organs other than the bone marrow, including the diverse functions of the transferrin receptor.

Dr. Iain Macdougall will briefly discuss the evolution of iron supplementation over the years, from direct parenteral administration of iron salts to the development of iron-carbohydrate complexes and iron nanoparticles. He will also discuss the latest translational science in the development of other iron supplementing strategies, including newer oral iron compounds, such as heme iron polypeptide, ferric citrate, and dialysate iron administration as ferric pyrophosphate citrate, as well as more indirect ways of increasing iron availability, such as a prolyl hydroxylase inhibition (phase III) and anti-hepcidin strategies (phase I and II).

Chair:

Martina Muckenthaler
University of Heidelberg
Heidelberg, Germany

Speakers:

Mark D. Fleming, MD, DPhil
Boston Children's Hospital
Boston, MA
Congenital Sideroblastic Anemias: Iron and Heme Lost in Mitochondrial Translation

Nancy C. Andrews, MD, PhD
Duke University School of Medicine
Durham, NC
Understanding the Transferrin Receptor and Cellular Iron Deficiency Outside the Erythron

Iain C. Macdougall, MD
King's College Hospital
London, United Kingdom
Iron Supplementation: What's New?

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Scientific Committee on Lymphoid Neoplasia

Advances in Cellular Immunotherapy for Lymphoid Malignancies

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg C- Lvl 1- Hall C4
Saturday, December 9, 2017
2:00 p.m. - 3:30 p.m.

Georgia World Congress Center, Bldg C- Lvl 1- Hall C1
Chimeric antigen receptor (CAR) T-cell immunotherapies offer promise for the effective treatment of lymphoid malignancies. Recent developments seek to improve the efficacy, specificity, response durability, and safety of CAR T-cell therapies and expand their therapeutic indications. 

Dr. Gianpietro Dotti will discuss the role of antigen selection and T-cell source in targeting hematologic malignancies using CARs. The field has been largely dominated by the adoptive transfer of T cells expressing the CD19-specific CAR in acute lymphoid leukemia and non-Hodgkin lymphomas. More recently, other target antigens have been tested in phase I studies with the aim of either mitigating the B-cell aplasia caused by CD19-specific CAR T cells in B-lymphoid malignancies or of targeting other malignancies non-expressing CD19. Two new targets, such as k-light chain of human immunoglobulins to target B-cell lymphomas and CD30 to target Hodgkin lymphoma, will be discussed. While polyclonal activated T cells are frequently used in clinical trials, other sources such as natural killer T cells can potentially be explored, and these will also be discussed.

Dr. Cameron Turtle will discuss response and toxicity data from a clinical trial studying immunotherapy in patients with B-cell malignancies using a defined composition of CD4+ and CD8+ CD19-targeted CAR T cells. Cytokine release syndrome and neurologic toxicity are complications that can occur in patients treated with CD19 CAR T cells. Our understanding of these syndromes is evolving, along with strategies to identify those at high risk of toxicity in whom early intervention or other mitigation strategies may be indicated.

Dr. Crystal Mackall will discuss the factors limiting the efficacy of CAR T-cell therapies, including primary and secondary resistance due to tumor-associated or T cell-associated factors. Antigen loss escape is a major factor associated with acquired resistance to CAR T-cell therapeutics. The biologic basis for such escape and approaches to diminish this phenomena will be discussed. T-cell exhaustion can also significantly limit the efficacy of CAR T-cell therapeutics. Recent insights into the biology of T-cell exhaustion and novel approaches to ameliorate this phenomena in the context of adoptive cell therapies will be discussed.

Chair:

Adolfo A. Ferrando, MD, PhD
Columbia University
New York, 

Speakers:

Gianpietro Dotti, MD
University of North Carolina
Chapel Hill, NC
Emerging T Cell Engineering Approaches: New Targets and New Cell Sources

Cameron J. Turtle, MBBS, PhD
Fred Hutchinson Cancer Research Center
Seattle, WA
Understanding Outcomes of CD19-Targeted CAR T Cell Immunotherapy

Crystal L. Mackall, MD
Stanford University
Stanford, CA
Enhancing the Efficacy of CAR T Cells

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Scientific Committee on Megakaryocytes and Platelets

New Innovations in Platelet Regulation of Tumor Growth and Metastasis

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 4- B401-B402
Sunday, December 10, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg C- Lvl 2- C202-C204
It has long been recognized that platelets play an important role in the regulation of tumor growth and metastasis into the vascular space. However, the underlying mechanisms by which the platelet-tumor interaction is mediated and how this aids in tumor extravasation and re-seeding has remained elusive. Platelets release a number of signaling proteins, molecules, and metabolites. In particular, the lipids released from the platelet help mediate tumor growth and metastasis in an ever-expanding and complex mechanism. Further, platelet extravasation into the tumor microenvironment is thought to play an extremely important role in tumor growth; and focal adhesion kinase (FAK) has recently been shown to be a driver in this process. A better understanding of these complex mechanisms will aid in future development of anti-platelet and/or anti-metastatic therapies limiting tumor growth and extravasation.

Dr. Tatiana Byzova will discuss platelet lipids and their regulation of tumor growth and metastasis, as well as recent findings.

Dr. Elisabeth Battinelli will discuss platelet angiogenic potential in platelet-mediated metastasis. Additionally, the role of tamoxifen in regulating this process will be discussed.

Dr. Anil Sood will discuss the role of platelet extravasation into the tumor microenvironment in stimulating tumor growth following cessation of anti-angiogenesis therapy. His talk will focus on FAK in platelets and its role in platelet migration into the tumor microenvironment.

Chair:

Michael Holinstat, PhD
University of Michigan
Ann Arbor, MI

Speakers:

Tatiana V. Byzova, PhD
Cleveland Clinic
Cleveland, OH
Reciprocal Interactions Between Platelets and Metastatic Tumors

Anil Sood, MD
The University of Texas MD Anderson Cancer Center
Houston, TX
Role of Platelets in Adaptive Changes to Anti-Angiogenesis Therapy

Elisabeth M. Battinelli, MD, PhD
Brigham and Women's Hospital
Boston, MA
Platelet and Megakaryocytic Regulation of Tumor Progression

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Scientific Committee on Plasma Cell Neoplasia

The Yin and Yang of Myeloma: Understanding and Harnessing Normal Plasma Cell Biology to Better Treat Myeloma

Sessions Offered Twice:
Saturday, December 9, 2017
7:30 a.m. - 9:00 a.m.

Georgia World Congress Center, Bldg C- Lvl 3- Georgia BR 1-3
Saturday, December 9, 2017
4:00 p.m. - 5:30 p.m.

Georgia World Congress Center, Bldg B- Lvl 5- Murphy BR 3-4
There has been great progress in the treatment of multiple myeloma, largely due to our ability to explore normal plasma cell biology through novel therapeutics. Plasma cells are committed to certain differentiation that creates vulnerabilities that are now being successfully exploited therapeutically as cancer treatments. Understanding this normal plasma cell biology has, therefore, become of paramount importance. Central to this understanding is the critically important process of protein metabolism and its associated signaling. In this session, speakers will review normal plasma cell biology as a way to better understand current paradigms for the treatment of myeloma.

Dr. Katia Georgopoulos will discuss the basic biology of normal plasma cells and how it is key to understanding the mechanisms of action of various anti-myeloma therapies. She will review the normal maturation process leading to long-lived plasma cells, including the key role played by Aiolos. Dr. Georgopoulos will also discuss the key role of Ikaros regulations of plasma cells and their interaction with the bone marrow microenvironment, a process that is likely critical for long-term survival.

Dr. Lawrence Boise will discuss the biology of protein homeostasis as it pertains to myeloma cell growth and survival. Like normal plasma cells, myeloma cells produce and secrete copious amounts of antibodies, a process that is reliant on quality control mechanisms within the cell. This includes the ubiquitin proteasome system, a key target of myeloma therapy. In addition to immunoglobulins, key proteins in plasma cell survival are regulated post-transcriptionally, including transcription factors and members of the BCL2 family. New findings and clinical implications of targeting protein homeostasis will be discussed.

Dr. Florian Bassermann will present recent mechanistic insights on cereblon (CRBN) functions and their link to metabolic processes such as the redox balance and lactate homeostasis. These insights will be discussed in the context of Immuno-modulatory drugs biology, the establishment of predictive biomarkers for IMiD response, and the design of new anti-myeloma drugs.

Chair:

Rafael Fonseca, MD
Mayo Clinic
Phoenix, AZ

Speakers:

Katia Georgopoulos, PhD
Massachusetts General Hospital
Boston, MA
Normal Plasma Cell Biology: Natural Achilles Heels as Targets in Myeloma

Lawrence H. Boise, PhD
Emory University
Atlanta, GA
Protein Homeostasis: A Key Target in Myeloma

Florian Bassermann, MD, PhD
Technical University of Munich
Munich, DEU
Cereblon and Redox in Plasma Cells

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Scientific Committee on Red Cell Biology

Editing and Enhancing Erythropoiesis

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 3- B312-B314
Sunday, December 10, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 3- B312-B314
This session will look at how the precise tools of gene editing and single cell transcriptomics are used to dissect the molecular mechanisms of normal and abnormal erythropoiesis, in turn facilitating targeted and finely tuned therapeutic approaches. 

Dr. Mitchell Weiss will discuss how genome editing can be used to manipulate genes or their regulatory elements in the treatment of hemoglobinopathies.

Dr. Jian Xu will discuss the application of gene editing tools and other genomic approaches to the study of erythroid transcriptional enhancers, uncovering their 3D-interactions in native chromatin.

Dr. Janis Abkowitz will discuss single cell transcriptomics and other approaches that highlight the tight coordination between heme and protein synthetic pathways in erythropoiesis. Its disruption underlies the anemia of Diamond Blackfan Anemia and myelodysplastic syndrome, an insight that can be used in therapy.

Chair:

Merav Socolovsky, MBBS, PhD
University of Massachusetts Medical School
Worcester, MA

Speakers:

Mitchell J. Weiss, MD, PhD
St. Jude Children's Research Hospital
Memphis, TN
Genome Editing Strategies to Treat Beta-Hemoglobinopathies

Jian Xu, PhD
University of Texas Southwestern Medical Center
Dallas, TX
In Situ Capture of the Molecular Composition of Erythroid Transcriptional Enhancers

Janis L. Abkowitz, MD
University of Washington
Seattle, WA
Delayed Globin Synthesis Leads to Excessive Heme and the Macrocytic Anemia of Diamond Blackfan Anemia and del(5q) Myelodysplastic Syndrome

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Scientific Committee on Stem Cells and Regenerative Medicine

Evolving Approaches to Gene Therapy for Blood Diseases

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 5- Murphy BR 3-4
Saturday, December 9, 2017
2:00 p.m. - 3:30 p.m.

Georgia World Congress Center, Bldg C- Lvl 1- Hall C4
A unique property of hematopoietic stem cells (HSCs) is their ability to generate all blood cell lineages for the lifetime of a recipient after HSC transplantation. Because of this, HSCs present an ideal target for many HSC gene therapy approaches for hemoglobinopathies, many immunodeficiencies, and other genetic disorders affecting the hematopoietic system. There has been tremendous progress in the development of vector systems for HSC gene therapy, with clear therapeutic benefit for some diseases. More recently, there has also been significant progress in gene editing technologies using various nuclease platforms. While there are many different approaches to modifying and correcting HSCs, the conditioning regimen has been a critical component for engraftment and persistence of HSCs and their progeny. The most current approaches use alkylating agents to facilitate engraftment, and in many cases, near-myeloablative doses are required for efficient engraftment and persistence of gene-modified and gene-corrected cells. While the use of alkylating agents have some advantages in eliminating or reducing any remaining cancer cells before transplantation, this would not be necessary or required for HSC gene therapy for genetic diseases. An ideal conditioning regimen for HSC gene therapy in patients with genetic diseases would be based on non-genotoxic reagents and conditions. Several approaches have recently been described and will be discussed in this session.

Dr. Philip Gregory will discuss advances in vector development and translation to clinical protocols and the role of gene editing technology for HSC gene therapy.

Dr. Hiromitsu Nakauchi will present a novel concept for non-genotoxic conditioning based on the role of valine in HSC maintenance and will discuss how valine restriction might facilitate HSC engraftment.

Dr. Judith Shizuru will discuss novel non-genotoxic conditioning approaches for HSC gene therapy using antibody-based conditioning.

Chair:

Hans-Peter Kiem, MD, PhD
Fred Hutchinson Cancer Research Center
Seattle, WA

Speakers:

Philip D. Gregory, DPhil
bluebird bio, Inc.
Cambridge, MA
Gene Therapy: Where We Started and Where the Field is Going

Hiromitsu Nakauchi, MD, PhD
University of Tokyo
Tokyo, Japan
Valine as a Key Metabolic Regulator of Hematopoietic Stem Cell Maintenance

Judith A. Shizuru, MD, PhD
Stanford University Medical Center
Stanford, CA
Novel Conditioning Regimens for Blood Stem Cell Transplantation

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Scientific Committee on Thrombosis and Vascular Biology

Thrombosis: A View From the World of Bioengineering

Sessions Offered Twice:
Saturday, December 9, 2017
7:30 a.m. - 9:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 2- B206
Sunday, December 10, 2017
7:30 a.m. - 9:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 2- B211-B212
In this session, speakers will review recent advances that allow more physiologic modeling of in vivo thrombosis as well as exciting engineering developments that may improve our ability to treat and/or prevent thromboembolism.

Dr. Wilbur Lam will describe how microchip-based technologies have enabled the development of “endothelialized” microfluidic devices to model clot formation under physiologic flow conditions in vitro. With the capability to recapitulate the shear forces and endothelial-blood cell interactions of the in vivo vascular microenvironment and inclusion of human and patient blood samples, these perfusable microsystems serve as versatile research-enabling and drug discovery platforms for hemostasis and thrombosis applications. In this session, seminal studies leveraging thrombosis-on-a-chip systems as well as recent advances and limitations of these technologies will be discussed

Dr. Keith Neeves will review experiments showing that low-strength magnetic fields can reversibly assemble wheel-shaped devices from individual colloidal building blocks and ablate thrombi using a combination of mechanical and chemical lysis. These wheel-shaped entities can then be driven, rotated, and directed along surfaces at velocities faster than most other microscale propulsion schemes. Possible future clinical applications of this concept will be discussed.

Dr. Jeffrey Lawson will describe vessels that are grown using banked human vascular cells and then de-cellularized so that they can be implanted into any patient, without tissue matching. These vessels have been evaluated in two phase II studies of patients with end-stage renal disease. The studies have shown that these vessels repopulate and remodel with host cells, can withstand multiple re-cannulations, and might have a resistance to infection comparable to that expected for native arteriovenous fistulas.

Chair:

David A. Garcia, MD
University of Washington
Seattle, WA

Speakers:

Wilbur A. Lam, MD,PhD
Emory University/Georgia Tech
Atlanta, GA
Thrombosis-on-a-Chip: A New Way to Model a Complex Process

Keith B. Neeves, PhD
Colorado School of Mines
Golden, CO
Magnetically Powered Microbots: A Novel Approach to Thrombolysis?

Jeffrey Lawson, PhD, MD
Duke University
Durham, NC
Engineered Blood Vessels

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Scientific Committee on Transfusion Medicine

Targeted for Destruction: Clearance and Hemostatic Activity of Endogenous and Transfused Platelets

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 2- B213-B214
Saturday, December 9, 2017
4:00 p.m. - 5:30 p.m.

Georgia World Congress Center, Bldg B- Lvl 4- B401-B402
Platelets play many different roles. Billions of platelets are produced daily, with complex mechanisms regulating production as well as clearance. Senescent, desialylated platelets are cleared through pathways involving the hepatic Ashwell-Morell receptor, whereas the spleen plays a key role in antibody-mediated platelet clearance. Although the majority of platelets transfused are currently stored at room temperature, refrigerated, cryo-preserved, and even freeze-dried platelets are showing metabolic and functional promise as transfusion products. This session will review endogenous and transfused platelets, from production to destruction.

Dr. Karin Hoffmeister will discuss mechanisms of endogenous platelet clearance, including the impact of this clearance on the regulation of thrombopoietin.

Dr. Andrew Cap will review storage options for platelets, and will discuss the impact of refrigerated storage, cryo-preservation, and lyophilization on cellular physiology.

Dr. John Semple will discuss the role that the spleen plays in platelet clearance and thrombocytopenia.

Chair:

Martin L. Olsson, MD, PhD
Lund University
Lund, Sweden

Speakers:

Karin M. Hoffmeister, MD
BloodCenter of Wisconsin
Milwaukee, WI
Novel Glycan Dependent Platelet Clearance Mechanisms

Andrew P. Cap, MD, PhD
U.S. Army Institute of Surgical Research
Fort Sam Houston, TX
Targeting Hemorrhage: Alternative Storage of Platelets for Hemostatic Transfusion

John W. Semple, PhD
Lund University
Lund, Sweden
Splenic Mechanisms of Thrombocytopenia

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Scientific Committee on Transplantation Biology and Cellular Therapies

Targeting T-Cell Exhaustion

Sessions Offered Twice:
Saturday, December 9, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 5- Murphy BR 1-2
Sunday, December 10, 2017
9:30 a.m. - 11:00 a.m.

Georgia World Congress Center, Bldg B- Lvl 5- Murphy BR 1-2
T cell exhaustion is the acquired state of dysfunction characteristic of the T cell response to cancer and chronic viral disease.  Efforts to reverse T cell exhaustion have led the development of immune checkpoint blockade therapies targeting, among others, the PD-1 immunoinhibitory receptor expressed by exhausted T cells.  Despite the dramatic clinical results with this new class of cancer therapies, only the minority of patients have sustained clinical benefit from ICB.  Thus improving cancer immunotherapy will require additional understanding of the differentiation of exhausted T cells and the role of the negative signaling molecules they express. 

Dr. Rafi Ahmed will review studies of the differentiation of T cells in response to acute and chronic viral pathogens and tumors.  He will describe recent developments that have led to the increased appreciation of functionally distinct subsets of exhausted T cells that help inform the rational design of immunotherapy aimed at reversing T cell exhaustion.

Dr. Arlene Sharpe will discuss the biology behind checkpoint blockade. She will focus on the immunoregulatory functions of the PD-1 pathway in regulating T cell activation, tolerance, resolution of inflammation, and anti-tumor immunity. She will discuss recent mechanistic studies that explain PD-1 pathway functions in cancer.

Dr. Dario Vignali will discuss the biology of the inhibitory receptor LAG3, and its contribution to T cell exhaustion and immune regulation on CD8+ and CD4+ intratumoral T cells in mouse models of cancer and autoimmunity, and in a variety of human malignancies.  He will also discuss the impact of LAG3 on regulatory T cell function.  He will also discuss how differential LAG3 expression could impact responsiveness to immunotherapy.

Chair:

W. Nicholas Haining, BM, BCh
Dana-Farber Cancer Institute
Boston, MA

Speakers:

Rafi Ahmed, PhD
Emory University Vaccine Center
Atlanta, GA
T-Cell Memory and Exhaustion

Arlene H. Sharpe, MD, PhD
Harvard Medical School
Boston, MA
Biology of PD-1 Checkpoint Blockade

Dario A.A. Vignali, PhD
University of Pittsburgh School of Medicine
Pittsburgh, PA
Biology of LAG3 Checkpoint Blockade

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