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Ad Hoc Scientific Committee on Bone Marrow Failure
DNA Damage, Cell Cycle, and Fanconi Anemia
| Sessions Offered Twice: |
December 8, 2012, 2:00 PM - 3:30 PM
Georgia World Congress Center (B206, Building B, Level 2, Georgia World Congress Center) | December 9, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B206, Building B, Level 2, Georgia World Congress Center) |
Fanconi anemia (FA) is an inherited bone marrow failure syndrome. Clinically, FA is characterized by a variety of congenital abnormalities and progressive bone marrow failure (BMF). Cells from FA patients have a striking hypersensitivity to DNA interstrand crosslinks, which has become the basis of a clinical diagnostic test for FA and is the basis of the genomic instability in patients with this condition. Among inherited bone marrow failure syndromes, FA has been the “poster child,” illustrating how insights into the pathogenetics and pathobiology directly impact diagnosis, care, and treatment of patients with FA. Furthermore, insights into the pathways of this rare genetic disease may lead to discovery of novel biological principles, such as the definition of a DNA repair pathway, with implications far beyond its own disease pathology.
Dr. Markus Grompe will review the phenotypic and genetic heterogeneity of FA, the genotype-phenotype correlations, and the pathways responsible for bone marrow failure. He will discuss how insight into these pathways provides novel therapeutic targets that may improve the severity of BMF or delay disease onset.
Dr. Stephen West will discuss how the FA proteins, encoded by genes that are mutated in FA, participate in the repair of DNA strand breaks and how mutations in these genes lead to genetic instability and cancer predisposition. He will demonstrate how the understanding of the disturbed pathways uncovers unexpected novel therapeutic options that might counterbalance the genomic stability and improve defective repair pathways in FA cells.
Dr. Ketan Patel will discuss exciting new insights into the link between metabolism and DNA damage and the consequences for potential new treatments.
Chair:
Monica Bessler, MD, PhD
University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Speakers:
Markus Grompe, MD
Oregon Health & Science University, Portland, OR, USA
Fanconi Anemia: Emerging Therapeutic Opportunities
Stephen C. West, PhD
Cancer Research UK, London, United Kingdom; London Research Institute, South Mimms, United Kingdom
Links Between Defective DNA Strand Break Repair and Genome Instability in Fanconi Anemia
Ketan J. Patel, PhD
Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom
Links Between DNA Damage and Metabolism, Pathways Causing Bone Marrow Failure in Fanconi Anemia, and Therapeutic Implications
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Ad Hoc Scientific Committee on Plasma Cell Neoplasia
Histone Modification in B-Cell Malignancies
| Sessions Offered Twice: |
December 8, 2012, 2:00 PM - 3:30 PM
Georgia World Congress Center (B308-B309, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B308-B309, Building B, Level 3, Georgia World Congress Center) |
This session will focus on understanding the distinct patterns of chromatin modifications and their impact on alterations in gene expression, the role of histone methylation in plasma cell and related malignancies, and targeting histone methyl transferases in myeloma. The session will also explore the functional role and therapeutic potential of the Bromodomain proteins associated with acetylated chromatin in myeloma.
Dr. Peter Jones will discuss the chromatin architecture and present an integrated view of the epigenome, including DNA methylation, histone modification, histone variants, and nucleosomal positioning, essential for chromatindependent signal transduction. He will also explain how these parameters change during the formation of most kinds of human cancers.
Dr. Jonathan Licht will review how histone methylation can be disrupted in multiple myeloma and related hematologic malignancies and how this affects cell growth, chromatin structure, gene expression, and DNA repair. He will also discuss how histone methyl transferases such as MMSET, rearranged and overexpressed in t(4;14)-associated myeloma, represent a therapeutic target in multiple myeloma.
Dr. James Bradner will discuss bromodomain and extraterminal (BET) subfamily of human bromodomain proteins (BRD 2-4) associated with acetylated chromatin. These proteins facilitate transcriptional activation by increasing the effective molarity of recruited transcriptional activators. Dr. Bradner will also discuss the impact of targeting bromodomain proteins in myeloma and their therapeutic application in B-cell malignancies.
Chair:
Nikhil C. Munshi, MD
Dana Farber Cancer Institute, Harvard Medical School, Boston VA Healthcare System, Boston, MA, USA
Speakers:
Peter A. Jones, PhD, DSc
University of Southern California, Los Angeles, CA, USA
Decoding the Chromatin Code
Jonathan D. Licht, MD
Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
Aberrant Histone Methylation in Myeloma: What Are the Rules?
James E. Bradner, MD
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Targeting Bromodomains in Myeloma
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Scientific Committee on Blood Disorders in Childhood
Misguided Myeloid Cells: From Inflammation to Malignancy
| Sessions Offered Twice: |
December 8, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B312-B313a, Building B, Level 3, Georgia World Congress Center) | December 8, 2012, 4:00 PM - 5:30 PM
Georgia World Congress Center (B312-B313a, Building B, Level 3, Georgia World Congress Center) |
This session will provide a bench-to-bedside overview of the histiocytic disorders Langerhans cell histiocytosis (LCH) and hemophagocytic lymphohistiocytosis (HLH). The emphasis of the basic science will be on the evolving understanding of intrinsic molecular lesions as well as the systemic immune dysregulation that underlie these disorders.
Dr. Miriam Merad will focus on the origin and function of myeloid dendritic cells. Specifically, she will focus on the significance of langerin+ cells (CD207), an antigen receptor with promiscuity and complexity beyond the epidermal Langerhans cell.
Dr. Carl Allen will discuss how recent molecular insights into the pathogenesis of LCH may redefine the disorder as a myeloid neoplasia and may affect future approaches to therapy.
Dr. Alexandra Filipovich will review the genetic mutations and functional immune defects that lead to unrestrained inflammation in hemophagocytic lymphohistiocytosis. She will also discuss novel diagnostic and therapeutic strategies, including promising results with stem cell transplant.
Chair:
Catherine M. Bollard, MD
Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital, Houston, TX, USA
Speakers:
Miriam Merad, MD, PhD
Mount Sinai School of Medicine, New York, NY, USA
The Origin and Function of Langerin (CD207) Expressing Cells in Mice and Humans
Carl E. Allen, MD, PhD
Baylor College of Medicine, Texas Children's Cancer and Hematology Centers, Houston, TX, USA
Langerhans Cell Histiocytosis: Back to Histiocytosis X
Alexandra H. Filipovich, MD
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Hemophagocytic Lymphohistiocytosis: Update of Biology and Treatment Options
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Scientific Committee on Hematopathology and Clinical Laboratory Hematology
New Insights into Blood Disorders from Sequencing of Genomes and Transcriptomes
| Sessions Offered Twice: |
December 8, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B313b-B314, Building B, Level 3, Georgia World Congress Center) | December 8, 2012, 2:00 PM - 3:30 PM
Georgia World Congress Center (B313b-B314, Building B, Level 3, Georgia World Congress Center) |
This session will focus on the scientific underpinnings and advances in blood disorder diagnosis from deep sequencing of the genome and transcriptome. Speakers will cover new insights that deep sequencing has provided into the diagnosis and pathogenesis of leukemias and B-cell disorders, with potential for translation into state-of-the-art clinical diagnostic testing and personalized medicine.
Dr. Elaine Mardis will provide a fundamental explanation of next-generation sequencing methods, including their strengths and weaknesses, for comprehensive genome and transcriptome analysis. She will provide pertinent examples of emerging uses of these technologies to address important clinical questions in leukemias, using her work as an example. Lastly, Dr. Mardis will present an illustrative scenario whereby genomic information about a patient’s leukemia can be used to better treat the disease, using each patient as a specific example in the spectrum of personalized medicine.
Dr. Torsten Haferlach will discuss the application of deep sequencing and the insights it has provided for both leukemias and other myeloid neoplasms. He will further discuss the translation of the discoveries into state-of-the-art clinical diagnostic testing for diagnosis and clinical management. Particularly, Dr. Haferlach will address how this novel laboratory method can be integrated into useful diagnostic algorithms.
Dr. Christian Steidl will describe the insights that whole-genome, exome, and transcriptome (RNA-seq) sequencing have provided for mature B-cell and T-cell lymphoproliferative disorders. Recent discoveries from lymphoid cancers will be highlighted; including both the novel insights into biology and the potential for clinical translation based on recurrent somatic mutations, novel fusion discovery, and targeted re-sequencing strategies.
Chair:
Catherine P. M. Hayward, MD, PhD
McMaster University, Hamilton, ON, Canada
Speakers:
Elaine R. Mardis, PhD
Washington University in St. Louis, St. Louis, MO, USA
Next-Generation Sequencing: A Discovery Tool for Blood Disorders
Torsten Haferlach, MD
MLL Munich Leukemia Laboratory, Munich, Germany
Next Generation Sequencing: Should it Become Part of Routine Diagnostics for Leukemias and Other Myeloid Neoplasms?
Christian Steidl, MD
British Columbia Cancer Agency, Vancouver, BC, Canada
Next-Generation Sequencing of Lymphoid Cancers: From Discovery to Clinical Translation
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Scientific Committee on Hematopoiesis
RNA Splicing in Normal and Malignant Hematopoiesis
| Sessions Offered Twice: |
December 8, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B308-B309, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B308-B309, Building B, Level 3, Georgia World Congress Center) |
This session will focus on recent discoveries of spliceosome mutations in myeloid malignancies and chronic lymphocytic leukemia (CLL) with the unexpected observation that mutations in the same gene are present in both myelodysplastic syndromes with ring sideroblasts and CLL. This session will begin with the basic aspects of RNA splicing, describe the spectrum of spliceosomal gene mutations, their biological consequences, their implications in disease prognosis, and the possibility of new therapeutic approaches.
Dr. Adrian Krainer will review the general mechanisms of RNA splicing and how splicing misregulation may lead to various diseases, including cell transformation. He will discuss the possibilities of new therapeutic strategies specifically targeting relevant alternative isoforms.
Dr. Seishi Ogawa will provide an overview of the genetic alterations in the splicing pathway in myeloid malignancies and their correlation with disease phenotypes. He will then present the consequences of these spliceosome mutations on RNA splicing and on the biology of hematopoietic cells, including stem cells.
Dr. Catherine Wu will present the results of next-generation sequencing in CLL. She will focus on the mutations in SF3B1, their consequences on splicing, and the new mechanistic insights provided by understanding the role of splicing on the pathogenesis of CLL. Dr. Wu will discuss the impact of these mutations on prognosis and treatment.
Chair:
William Vainchenker, MD, PhD
Institut National de la Santé et de la Recherche Médicale, Institut Gustave-Roussy, Villejuif, France
Speakers:
Adrian Krainer, PhD
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
Pre-mRNA Splicing Mechanisms, Misregulation in Disease, and Therapeutic Strategies
Seishi Ogawa, MD, PhD
Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Pathway Mutations in the Splicing Machinery in Myeloid Neoplasms
Catherine J. Wu, MD
Dana-Farber Cancer Institute, Boston, MA, USA
Understanding the Role of Mutations in SF3B1 and Splicing in Chronic Lymphocytic Leukemia
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Scientific Committee on Hemostasis
New Aspects of von Willebrand Factor Biology
| Sessions Offered Twice: |
December 8, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B401-B402, Building B, Level 4, Georgia World Congress Center) | December 9, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B401-B402, Building B, Level 4, Georgia World Congress Center) |
Over the past few years there have been significant advances in our understanding of the structure and function of von Willebrand factor (vWF) and its regulation by the vWF cleaving protease ADAMTS13. This session will highlight new findings in these areas and their implications in hemostasis and thrombosis.
Dr. Timothy Springer will discuss new molecular and biophysical studies of vWF. Recent electronic microscopy structures provide insight into the domain architecture of vWF and the basis for its flexibility. The extraordinary length of vWF allows it to act as a sensor of vascular flow. Dr. Springer will also provide new insights into how forces acting on vWF affect its function, including in types 2A and 2B von Willebrand disease.
Dr. Cécile Denis will provide an overview of recent advances in identifying novel pathways regulating vWF function. She will discuss results from in vitro studies and in vivo approaches using dedicated animal models.
Dr. Long Zheng will discuss new findings in the structural components of ADAMTS13 required for productive cleavage of vWF. He will also describe the cofactor-dependent regulation of ADAMTS13 function in vitro and in vivo using animal models.
Chair:
Barbara A. Konkle, MD
Puget Sound Blood Center, University of Washington, Seattle, WA, USA
Speakers:
Timothy A. Springer, PhD
Children's Hospital Boston, Boston, MA, USA
Activation of A1 Domain Adhesiveness in von Willebrand Factor by Elongational Force
Cécile V. Denis, PhD
Institut National de la Santé et de la Recherche Médicale, Le Kremlin-Bicêtre, France
Determinants of von Willebrand Factor Function
X. Long Zheng, MD, PhD
The Children's Hospital of Philadelphia, Philadelphia, PA, USA; The University of Pennsylvania, Philadelphia, PA, USA
von Willebrand Factor-ADAMTS13 Interactions
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Scientific Committee on Immunology and Host Defense
Immune Cells Bridging Innate and Adaptive Immunity
| Sessions Offered Twice: |
December 8, 2012, 2:00 PM - 3:30 PM
Georgia World Congress Center (B312-B313a, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B312-B313a, Building B, Level 3, Georgia World Congress Center) |
This session will explore the widening knowledge of the cellular players at the interface between the innate and adaptive immune systems. Special focus will be placed on the discussion of innate lymphoid cells, invariant natural killer cells, and dendritic cells, with particular attention to notions deriving from studies in human cells.
Dr. Hergen Spits will discuss the multifaceted functions of innate lymphoid cells, a novel and expanding family of immune effector cells that serve multiple roles including lymphoid tissue formation in embryogenesis, immune protection from microorganisms, and tissue remodeling after infection or inflammatory injury.
Dr. Madhav Dhodapkar will focus his presentation on the latest understanding of diversity and functional properties of lipidreactive natural killer T cells and the potential of harnessing the properties of these cells in clinical studies for cancer treatment.
Dr. Young will give an update on dendritic cell biology, focusing on the heterogeneity between dendritic cell subsets and the implications for innate and adaptive immune responses.
Chair:
Fabio Candotti, MD
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Speakers:
Hergen Spits, PhD
Tytgat Institute for Intestinal and Liver Research, Academic Medical Center at the University of Amsterdam, Amsterdam, Netherlands
New Insights in Development and Function of Human Innate Lymphoid Cells
Madhav V. Dhodapkar, MD
Yale University, New Haven, CT, USA
Harnessing Invariant Natural Killer T Cells for Cancer Therapy
James W. Young, MD
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Human Dendritic Cell Heterogeneity: Opportunities and Challenges for the Control of Immunity
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Scientific Committee on Iron and Heme
Orchestration of Systemic Iron Balance
| Sessions Offered Twice: |
December 8, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B312-B313a, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B312-B313a, Building B, Level 3, Georgia World Congress Center) |
This session will focus on the three major organs involved in orchestrating systemic iron balance: the liver, the intestine, and the erythron. The role of each of these organs and their interactions will be reviewed, including normal control mechanisms in health and alterations in disease. Recent advances in understanding hereditary disorders associated with abnormal iron homeostasis and therapeutic implications will be discussed in relation to conditions such as hemochromatosis, the thalassemias, and ironrefractory iron deficiency anemia.
Dr. Herbert Lin will present recent research on hepatic iron sensing and how the liver acts as the conductor of systemic iron regulation through the BMP signaling pathway that controls production of hepcidin. A review of current knowledge about the regulation of hepcidin expression will be presented, including the effects of altered iron stores, inflammation, and hereditary disorders.
Dr. Carole Peyssonnaux will focus on the role of hepcidin in the normal control of intestinal iron absorption and variations associated with disorders, such as increased ineffective erythropoiesis and hypoxia. The roles of HIF2á, duodenal iron transporters (DMT1, ferroportin), and duodenal ferritin in regulation of iron transport across the duodenal mucosa will also be explored.
Dr. Yelena Ginzburg will discuss modulation of hepcidin expression by erythropoiesis both under normal conditions and in disease states associated with increased ineffective erythropoiesis, including the role of humoral erythropoietic factors that influence hepcidin regulation and thereby control the iron supply from both the reticuloendothelial system and dietary sources.
Chairs:
Gordon D. McLaren, MD
University of California, Irvine, CA
Gordon D. McLaren, MD
University of California, Irvine, Orange, CA, USA; Department of Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA
Speakers:
Herbert Yih-Fuu Lin, MD, PhD
Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
The Liver as a Conductor of Systemic Iron Regulation: the Central Role of Hepcidin and BMP Signaling
Carole Peyssonnaux, PhD
Institut National de la Santé et de la Recherche Médicale, Paris, France
The Gut: Role at Steady State and Variations in Disordered Conditions
Yelena Ginzburg, MD
New York Blood Center, New York, NY, USA
The Red Cell: How Erythropoiesis Modulates Hepcidin Expression
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Scientific Committee on Lymphoid Neoplasia
B-Cell Receptor Signaling in the Pathogenesis and Treatment of Lymphoid Malignancy
| Sessions Offered Twice: |
December 8, 2012, 4:00 PM - 5:30 PM
Georgia World Congress Center (B302-B303, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B302-B303, Building B, Level 3, Georgia World Congress Center) |
The speakers in this session will highlight recent advances in understanding the role of B-cell receptor (BCR) signaling in the pathogenesis of B-cell malignancies and the potential of targeting abnormal BCR signaling for therapeutic purposes.
Dr. Freda Stevenson will discuss the role of BCR signaling in chronic lymphocytic leukemia (CLL), based on evidence that ligand-induced modulation of surface immunoglobulin M (IgM) contributes to the pathogenesis of this malignancy by engaging downstream proliferative and anti-apoptotic pathways. New observations on the intraclonal heterogeneity in selective IgM expression important for therapeutic targeting also will be described.
Dr. Louis Staudt will summarize how the use of functional and structural genomics revealed that the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) relies on a “chronic active” form of BCR signaling for survival. Therapies targeting chronic active BCR signaling have significant clinical activity in relapsed/refractory ABC DLBCL. Other human lymphoma subtypes also rely on constitutive BCR signaling for survival but engage this pathway in a mechanistically distinct fashion. The expanding potential of BCR-directed therapies in human lymphomas will be discussed.
Dr. John Byrd will explain how novel targeted therapies directed at BCR signaling produce a high rate of durable responses in both low-grade lymphoma and CLL. Remarkably, these agents have produced very modest toxicity that has allowed prolonged continuous dosing of medication and prolonged remissions. Many questions remain relative to the integration of these agents into routine clinical practice that will be reviewed during this session.
Chair:
Clark W. Distelhorst, MD
Case Western Reserve University, Cleveland, OH, USA
Speakers:
Freda K. Stevenson, DPhil
University of Southampton, Southampton, United Kingdom
B-Cell Receptor Signaling in Chronic Lymphocytic Leukemia
Louis M. Staudt, MD, PhD
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Chronic Active B-Cell Receptor Signaling in Lymphoma
John C. Byrd, MD
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Therapeutic Targeting of B-Cell Receptor Signaling Pathways
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Scientific Committee on Myeloid Biology
Role of HOX Genes in Normal and Malignant Hematopoiesis
| Sessions Offered Twice: |
December 8, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B302-B303, Building B, Level 3, Georgia World Congress Center) | December 8, 2012, 2:00 PM - 3:30 PM
Georgia World Congress Center (B302-B303, Building B, Level 3, Georgia World Congress Center) |
HOX proteins are central regulators of hematopoietic stem cells and hematopoietic differentiation. Groups of HOX proteins are expressed in a differentiation stage-specific manner during hematopoiesis. Anterior HOX proteins (HOX1-4) are expressed predominantly in hematopoietic stem cells and posterior HOX proteins (HOX7-11) are expressed in committed progenitors. Moreover, HOX genes are critical for the pathogenesis of myeloid malignancies and are the target of some of the genetic lesions that drive leukemogenesis. This session will review the role of HOX gene regulation in both normal and malignant myelopoiesis.
Dr. Patricia Ernst will discuss the role of MLL1 and its downstream targets, including Hox genes, in coordinating hematopoietic stem cell self-renewal with proliferation. The mechanisms by which MLL1 controls the expression of its target genes will be considered, including the role of chromatin targeting and catalytic activities in maintaining different categories of genes required for normal hematopoiesis.
Dr. Elizabeth Eklund will discuss the role that posterior HOX proteins play in progenitor expansion and differentiation focusing on target genes for Hoxa9 and Hoxa10. Cooperative and antagonistic functions of these transcription factors in controlling myeloid progenitor expansion and differentiation will be considered.
Dr. Jay Hess will discuss emerging evidence suggesting that Hoxa9, which is overexpressed in more than half of myeloid acute leukemias, modulates the activity of lineage-specific enhancers controlling a network of proleukemogenic target genes.
Chair:
Emmanuelle Passegué, PhD
University of California - San Francisco, San Francisco, CA, USA
Speakers:
Patricia Ernst, PhD
Dartmouth College, Hanover, NH, USA
Coordinating Self-Renewal and Proliferation via MLL1-HOX Pathways and Beyond
Elizabeth A. Eklund, MD
Northwestern University Feinberg School of Medicine and Jesse Brown VA Medical Center, Chicago, IL, USA
Regulation of Myelopoiesis by Differentiation Stage-Specific Activities of HOXA9 and HOXA10
Jay L. Hess, MD, PhD, MHSA
University of Michigan Medical School, Ann Arbor, MI, USA
Mechanisms of Transcriptional Regulation and Transformation by HOXA9
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Scientific Committee on Myeloid Neoplasia
Personalized Diagnostics in Acute Myeloid Leukemia and Myelodysplasia
| Sessions Offered Twice: |
December 8, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B302-B303, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B302-B303, Building B, Level 3, Georgia World Congress Center) |
A major challenge in clinical medicine and biomedical research is to integrate current knowledge and technological advances into the best care for each individual patient. Genomic technologies have transformed our understanding of the genetic basis of myeloid malignancies, and it is expected that a new disease taxonomy that incorporates existing clinical parameters with data about mutations – and potentially epigenomic, metabolomic, and microbiomic research – will provide accurate and precise definitions of diseases and opportunities for specific treatment modalities and improved individual health outcomes. This evolutionary process requires that patients, communities, and diseases be considered together and will demand new biomedical paradigms whereby physical and biological scientists and clinicians work closely to answer health-related questions. This session will focus on examining opportunities for translating new knowledge from different sources in the management of acute myeloid leukemia and myelodysplasia.
Dr. Benjamin Ebert will discuss the clinical impact of point-mutations in myelodysplastic syndromes, and how genetic data can be used to improve the prediction of prognosis and response to therapy.
Dr. Matthew Walter will discuss the clonal architecture of myelodysplastic syndromes and the clinical implications of whole genome sequencing.
Dr. Bob Löwenberg will discuss how a multitude of emerging potentially relevant molecular biomarkers are creating a growing informative prognostic background that can be used for risk-adapted therapy decisions.
Chair:
Raul Ribeiro, MD
St. Jude Children's Research Hospital, Memphis, TN, USA
Speakers:
Benjamin L. Ebert, MD, PhD
Brigham and Women's Hospital, Harvard Medical College, Boston, MA, USA
Discovery Science and Integrating Molecular Diagnosis into Clinical Practice
Matthew J. Walter, MD
Washington University in St. Louis, St. Louis, MO, USA
Biology of Myelodysplasia Clonality: Clinical Implications of Whole-Genome Sequencing
Bob Löwenberg, MD, PhD
Erasmus Medical Center, Rotterdam, Netherlands
The Impact of Novel Molecular Markers on Risk Stratification in Acute Myeloid Leukemia
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Scientific Committee on Platelets
Secrets of Secretion
| Sessions Offered Twice: |
December 8, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B401-B402, Building B, Level 4, Georgia World Congress Center) | December 8, 2012, 4:00 PM - 5:30 PM
Georgia World Congress Center (B401-B402, Building B, Level 4, Georgia World Congress Center) |
This session will provide an overview of secretory processes in megakaryocytes and platelets. Emphasis will be placed on how granules are formed in megakaryocytes and how constituents are packaged into granules and released upon activation. Evolving concepts on the homogeneity and/or heterogeneity of a-granules in platelets will also be addressed and discussed.
Dr. Walter Kahr will focus on the genetic and biochemical triggers of granular formation in megakaryocytes and platelets. His presentation will include discussion of mutations in VPS33B
and NBEAL-2 that are the genetic causes of abnormal a-granule formation in arthrogryposis, renal dysfunction and cholestasis, and gray platelet syndrome, respectively.
Dr. Joseph Italiano will discuss the release of proteins from platelet a-granules that modulate angiogenic processes. His discussion will also shed light on how differential release of angiogenic factors from platelets may provide a new modality for the treatment of cancer.
Dr. Sidney Whiteheart will discuss the patterns of a-granule cargo release in response to differential platelet activation. He will also review the molecular mechanisms underlying the platelet release reaction and speculate on how these steps may be viable targets for anti-thrombotic therapies.
Chair:
Andrew S. Weyrich, PhD
The University of Utah, Salt Lake City, UT, USA
Speakers:
Walter H. Kahr, MD, PhD
The Hospital for Sick Children, Toronto, ON, Canada
Molecular Triggers of Granule Formation in Megakaryocytes and Platelets
Joseph E. Italiano Jr., PhD
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
New a-Granule Biology Reveals How Platelets May Regulate Angiogenesis
Sidney W. Whiteheart, PhD
University of Kentucky, Lexington, KY, USA
Temporal Secretion of a-Granular Products: Insights into the Mechanisms of Release Reaction
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Scientific Committee on Red Cell Biology
How to Make a Red Blood Cell
| Sessions Offered Twice: |
December 8, 2012, 4:00 PM - 5:30 PM
Georgia World Congress Center (B313b-B314, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B313b-B314, Building B, Level 3, Georgia World Congress Center) |
This session will focus on recent progress in the understanding of developmental erythropoiesis, advances in induced pluripotent stem cells, and the use of stem cell precursors in the expansion and production of erythrocytes.
Dr. James Palis will review aspects of red blood cell development including embryonic, fetal, and adult erythropoiesis. His laboratory has made significant advances in understanding the ontogeny of fetal erythropoiesis.
Dr. Igor Slukvin will discuss the development of induced pluripotent stem cells and describe optimization of conditions for the optimal production of differentiated red blood cells. Development of red blood cells from a defined progenitor has several advantages, including minimizing risk of transfusion reactions such as graft-versus-host disease. Dr. Slukvin will also discuss the emerging ethical and societal issues involved in utilizing an engineered blood product.
Dr. Luc Douay will report his exciting findings in the production of large quantities of red blood cells from CD34-positive precursors. His laboratory has shown that cultured red blood cells are functional when introduced into an immunodeficient mouse. Furthermore, Dr. Douay’s team illustrated that labeled cultured blood cells had a comparable half-life when injected into a volunteer. Dr. Douay will also provide perspectives on future directions in the use of progenitor cell, cord blood, and pluripotent stem cell technologies that have the potential to transform regenerative medicine.
Chair:
Dwayne Barber, PhD
Ontario Cancer Institute, Toronto, ON, Canada
Speakers:
James Palis, MD
University of Rochester Medical Center, Rochester, NY, USA
Primitive and Definitive Erythropoiesis
Igor Slukvin, MD, PhD
University of Wisconsin, Madison, WI, USA
Induced Pluripotent Stem Cells and Erythrocyte Production
Luc Douay, MD, PhD
Université Pierre et Marie Curie, Paris, France
In Vitro Production of Erythrocytes
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Scientific Committee on Stem Cells and Regenerative Medicine
Stressed-Out Stem Cells
| Sessions Offered Twice: |
December 8, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B308-B309, Building B, Level 3, Georgia World Congress Center) | December 8, 2012, 4:00 PM - 5:30 PM
Georgia World Congress Center (B308-B309, Building B, Level 3, Georgia World Congress Center) |
Hematopoietic stem cells (HSCs) continuously replenish the peripheral blood at a steady rate during normal conditions. The hematopoietic system is highly flexible, with effector cell production augmented and restrained as needed. Recently, the role of hematopoietic stem cells in responding to these changing demands has become increasingly appreciated.
This session will focus on the types of stresses HSCs experience, their response to stress, and the mechanisms involved in these responses. Individual presentations will elaborate on the highly dynamic role that stem cells play in hematologic homeostasis, as well as the regulatory mechanisms and the key questions that will shape research in the coming years.
Dr. Markus Manz will review the impact of infection on the effector, progenitor, and stem cell populations.
Dr. Andreas Trumpp will focus on the signaling molecules that enable the HSC response, particularly interferons.
Dr. Toshio Suda will focus on the unique metabolic status of HSCs and the changes that occur in HSC metabolism during the stress response.
Chairs:
Margaret A. Goodell, PhD
Baylor College of Medicine, Houston, TX, USA
George Q. Daley, MD, PhD
Children's Hospital Boston and Howard Hughes Medical Institute, Boston, MA, USA
Speakers:
Markus G. Manz, MD
University Hospital Zürich, Zürich, Switzerland
Microbial Impact on Hematologic Homeostasis
Andreas Trumpp, PhD
German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Heidelberg, Germany
Stress-Mediated Activation of Dormant Hematopoietic Stem Cells In Vivo
Toshio Suda, MD
School of Medicine, Keio University, Tokyo, Japan
Metabolic Regulation of Hematopoietic Stem Cells During Stress
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Scientific Committee on Thrombosis and Vascular Biology
Initiation of Thrombus Formation During the Innate Immune Response
| Sessions Offered Twice: |
December 8, 2012, 2:00 PM - 3:30 PM
Georgia World Congress Center (B401-B402, Building B, Level 4, Georgia World Congress Center) | December 9, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B401-B402, Building B, Level 4, Georgia World Congress Center) |
Emerging evidence from animal models and clinical studies supports close connections between immune responses to tissue injury/ insult and pathways involved in thrombosis. The interplay between the innate immune system, platelets, and the coagulation cascade may promote host-defense responses and tissue repair. It may also contribute to progression of disease processes such as atherosclerosis, autoimmune disorders, inflammatory lung and bowel disorders, and obesity. This session will provide the latest scientific evidence of the molecular mechanism(s) underlying these interactions and, when known, their pathophysiologic consequences.
Dr. Hartmut Weiler will discuss the fact that activated protein C (APC) – although initially demonstrating promise in reducing mortality in sepsis – exerts complex effects that alter its efficacy as a therapeutic agent. In preclinical models, the sepsis mortality reduction by APC involves signaling through protease-activated receptors, the endothelial protein C receptor, and integrins. Additionally, APC may interact with novel substrates such as histones and tissue factor pathway inhibitor to control coagulation and inflammation. Such receptor interactions may determine the biological response to endogenous and therapeutically administered APC.
Dr. Thomas McIntyre will briefly summarize the ability of platelets to splice and translate RNA and the pathways involved. He will then discuss how endotoxin promotes the synthesis and release of proinflammatory cytokines, such as IL1ß, from platelets.
Dr. Fahumiya Samad will briefly review the links between obesity, inflammation, and thrombosis. In particular, she will focus on new evidence that tissue factor (TF) may have coagulation-independent functions in promoting obesity and its consequences. Dr. Samad will also describe the contributions of TF and PAR2 to diet-induced obesity and the molecular mechanism(s) responsible.
Chair:
Susan S. Smyth, MD, PhD
University of Kentucky, Lexington, KY, USA
Speakers:
Hartmut Weiler, PhD
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA
Activated Protein C, Sepsis, and the Innate Immune Response to Infection
Thomas M. McIntyre, PhD
Cleveland Clinic Lerner Research Institute, Cleveland, OH, USA
Inflammatory Cytokines and Thrombosis
Fahumiya Samad, PhD
Torrey Pines Institute for Molecular Studies, San Diego, CA, USA
Inflammation, Obesity, and Thrombosis
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Scientific Committee on Transfusion Medicine
Toxicologic Effects of Blood Transfusion
| Sessions Offered Twice: |
December 8, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B206, Building B, Level 2, Georgia World Congress Center) | December 9, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B206, Building B, Level 2, Georgia World Congress Center) |
This session will focus on recent developments in our understanding of potential toxicities that may be inadvertently generated as a result of storing blood and blood products prior to transfusion.
Dr. Eldad Hod will speak about the effects of transfusing stored red blood cells on infection and inflammation. Both animal and human data will be discussed, with a focus on how iron and iron biology may play a mechanistic role in influencing this process.
Dr. Nilam Mangalmurti will discuss the specific chemical class that accumulates both naturally and also in stored blood products called advanced glycation endproducts. The role that such chemical moieties play in potential toxicity of blood products will be discussed with a focus on biological interactions with vascular endothelium.
Dr. Christopher Silliman will discuss how proinflamamtory lipid entities (eicosanoids and lysophospholipids) are generated during blood storage and discuss the biological sequelae of transfusing products containing such entities.
Chair:
James C. Zimring, MD, PhD
Puget Sound Blood Center, University of Washington, Seattle, WA, USA
Speakers:
Eldad A. Hod, MD
Columbia University Medical Center, New York, NY, USA
The Role of Iron in Toxicity of Stored Red Blood Cell Units
Nilam S. Mangalmurti, MD
University of Pennsylvania, Philadelphia, PA, USA
Erythrocyte Advanced Glycation End-Products as Novel Mediators of Endothelial Dysfunction Following Transfusion
Christopher C. Silliman, MD,PhD
Bonfils Blood Center, Denver, CO, USA
Lipids: Free Fatty Acids, Eicosanoids, and Lysophospholipids and the Pro-Inflammatory Effects of Transfusion
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Scientific Committee on Transplantation Biology
Microbiota, Gut Inflammation, and Transplantation: Back to the Future
| Sessions Offered Twice: |
December 8, 2012, 9:30 AM - 11:00 AM
Georgia World Congress Center (B313b-B314, Building B, Level 3, Georgia World Congress Center) | December 9, 2012, 7:30 AM - 9:00 AM
Georgia World Congress Center (B313b-B314, Building B, Level 3, Georgia World Congress Center) |
With the advent of novel methodologies, studies regarding human microbiota have made remarkable progress in the elucidation of the role of microbes in human health and disease. Inflammatory bowel disease (IBD) is an ideal setting for such studies, as disruption of homeostasis between the host immune system and the gut microbiota is central to IBD pathogenesis. The pathophysiology of intestinal graft-versus-host disease (GVHD) has many similarities with IBD. This session will review recent developments in the study of microbiota, IBD, and intestinal GVHD.
Dr. Wendy Garrett will discuss how specific microbes can instigate, promote, or inhibit colitis through their effects on the mucosal immune system or the microbial communities in the gut. Chronic inflammation in the intestine is also an important risk factor for colorectal cancer. Ongoing work on the colorectal microbiome using experimental models and human tumors will be discussed, as well as the potential benefits for beneficial microbes and functional foods in the context of these diseases.
Dr. Ernst Holler will review the role of molecules involved in immune defense against microbiota, especially NOD2/CARD 15. Polymorphisms within these genes have been identified as risk factors of inflammatory bowel disease, but have also been more recently associated with intestinal GVHD following allogeneic stem cell transplantation and rejection in small bowel transplantation. Potential mechanisms, such as altered antibacterial peptides – mainly defensins – as well as responses, microbiome changes, and altered recruitment of protective intestinal T cells will be discussed and linked to the increased activation of the T-cell response.
Dr. Robert Jenq will review the relationship between the intestinal bacterial flora and GVHD. He will then discuss the recent studies on the cross-talk between the intestinal microbiota, nutrition, and intestinal inflammation in murine and human recipients of allogeneic hematopoietic stem cell transplants.
Chair:
Marcel R.M. van den Brink, MD, PhD
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Speakers:
Wendy S. Garrett, MD, PhD
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Harvard School of Public Health, Boston, MA, USA
Gut Microbiota and Intestinal Inflammation
Ernst Holler, PhD
University of Regensburg Medical Center, Regensburg, Germany
Intestinal Microbiota: From Inflammatory Bowel Disease to Bone Marrow Transplantation
Robert R. Jenq, MD
Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Intestinal Microbiota in Bone Marrow Transplantation
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