Scientific Spotlight Sessions

Fulfilling the Promise: Pluripotent Stem Cells as Models for Human Blood Development and Disease

Monday, December 9, 2024, 2:45 p.m. - 4:00 p.m.
San Diego Convention Center, Room 31

(hPSCs) for transplantation and disease modeling has been a long-standing goal in the field. In recent years there has been tremendous progress in the field, and investigators have been able to define the developmental cues to direct mesodermal differentiation to definitive HSC fate rather than to embryonic yolk sac-type progenitors. These studies have been largely enabled by the advances in single-cell transcriptomic technologies, permitting comparison of in vitro HSC derivation to human HSCs developing in situ in the embryo. The ability to translate our better appreciation of HSC development in the human embryo into the development of in vitro differentiation protocols has resulted in the generation of multilineage engrafting HSCs (iHSCs) from human induced pluripotent stem cells (iPSCs), a recent and significant advance in the field. In parallel, in recent years, a variety of hPSC models, mainly based on iPSC, have been developed for a variety of non-malignant and malignant blood diseases. These have been shown to recapitulate key disease features both in vitro and in vivo in xenograft assays and have empowered unprecedented interrogation into the pathogenesis and therapeutic targeting of hematologic diseases. Advances in these areas of research will be highlighted in this session.

Co-Chairs:

Elizabeth S. Ng, PhD
Murdoch Childrens Research Institute
Parkville, Melbourne, VIC, Australia

Eirini Papapetrou, MD,PhD
Icahn School of Medicine at Mount Sinai
New York, NY

Speakers:

Elizabeth W. Ng, MD
Kansas City Cancer Center
Overland Park, KS
Hematopoietic Stem Cell Development from Human Pluripotent Stem Cells

Eirini Papapetrou, MD,PhD
Icahn School of Medicine at Mount Sinai
New York, NY
Modeling Blood Disorders Using Human Pluripotent Stem Cells

Biology Underlying Disparities in Lymphoid Malignancies

Sunday, December 8, 2024, 4:30 p.m. - 5:45 p.m.
Marriott Marquis San Diego Marina, Pacific Ballroom Salons 18-19

This session will focus on uncovering how disparities in lymphoid cancers may be influenced by both the tumor microenvironment and genetic sequencing. By examining different types of lymphomas, the speakers will highlight how biological and genetic factors contribute to the disparities observed in Hodgkin lymphoma, multiple myeloma, and non-Hodgkin lymphoma for specific populations. This session aims to provide a comprehensive understanding of how these factors interact and shape treatment responses, survival rates, and disease progression, offering insights into reducing healthcare inequities. Together, these presentations will underscore the importance of a multifaceted approach—encompassing both the tumor environment and genetic profiling—to tackling disparities in lymphoma treatment and outcomes.

Dr. Cozen will discuss the critical role the tumor microenvironment plays in influencing disease outcomes, specifically focusing on how immune cells, stromal cells, and signaling molecules create conditions that vary across multiethnic cohorts. The presentation will explore how these variations may contribute to the disparities seen in survival and treatment response in both Hodgkin lymphoma and multiple myeloma. She will also present recent findings that suggest the microenvironment's interaction with genetic and socioeconomic factors, shaping future approaches for research and interventions for these populations.

Dr. Flowers will delve into the role of tumor sequencing in identifying genetic mutations and biomarkers that may be disproportionately prevalent across ancestry groups. The presentation will also discuss the relationships between genomic data and disease phenotypes that can be modeled and may impact treatment efficacy and outcomes. He will discuss the implications of these findings for precision medicine, including the need for more inclusive genetic research to better understand and address these disparities.

Co-Chairs:

Christopher R. Flowers, MD, MS
The University of Texas MD Anderson Cancer Center
Houston, TX

Wendy Cozen, DO, MPH
UCI, School of Medicine
Orange, CA

Speakers:

Christopher R. Flowers, MD, MS
The University of Texas MD Anderson Cancer Center
Houston, TX
Tumor Sequencing to Investigate Disparities in Non-Hodgkin Lymphoma

Wendy Cozen, DO, MPH
UCI, School of Medicine
Orange, CA
Tumor Microenvironment Profiling to Investigate Disparities in Hodgkin Lymphoma and Multiple Myeloma

Inflammation as a Regulator of Hematopoietic Homeostasis in Disease and Clonal Selection

Sunday, December 8, 2024, 4:30 p.m. - 5:45 p.m.
San Diego Convention Center, Room 7

Hematopoietic stem and progenitor cells (HSPCs) are responsible for sensing and integrating infectious/inflammatory cues into hematopoietic responses in bone marrow and producing hemato-immune cells at high demand in peripheral tissues. This session will describe how the pro-inflammatory environment/response and systemic inflammation act on and subsequently shape hematopoietic development, homeostasis and diseases. 

Dr. Serine Avagyan will discuss the role of inflammatory pathways in developmental origins of HSPCs, and in shaping postnatal hematopoiesis in the context of aging and genetic blood disorders. This talk will highlight recent studies investigating how inflammation affects the fate of normal and mutant HSPCs, and the pathways by which inflammatory exposure affects the selection of mutant HSPC clones due to differential clonal fitness.   

Dr. Hitoshi Takizawa will discuss an interplay between hematopoiesis and commensal bacteria, a symbiont increasingly recognized as an important modulator for hematopoiesis in health and disease. This session will highlight recent cutting-edge research deciphering pathways by which commensal bacteria and their-derived signals influence the hematopoietic programs, hemato-immune aging, stem cell clonal diseases, and thereby, discuss future preemptive/therapeutic strategies.

Co-Chairs:

Hitoshi Takizawa, PhD
Kumamoto University
Kumamoto City, Japan

Serine Avagyan, MD,PhD
University of California San Francisco
San Francisco, CA

Speakers:

Hitoshi Takizawa, PhD
Kumamoto University
Kumamoto, Japan
Inflammation As a Regulator of Hematopoietic Homeostasis in Disease

Serine Avagyan, MD,PhD
University of California San Francisco
San Francisco, CA
Inflammation As a Regulator of Hematopoietic Homeostasis in Clonal Selection

Iron at the Crossroads Between Erythropoiesis and Megakaryopoiesis

Monday, December 9, 2024, 2:45 p.m. - 4:00 p.m.
San Diego Convention Center, Room 30

Iron balance is critical for healthy and effective erythropoiesis and thrombopoiesis. All mammalian cells rely on iron and the erythropoietic compartment consumes especially high quantities of iron for hemoglobin synthesis. Effective crosstalk is essential for optimal red cell and platelet production. This session will discuss how heme and iron deficiency, excess, trafficking, and processing contribute to ineffective erythropoiesis and anemia and contribute to red cell and platelet production in JAK2 mutant myeloproliferative neoplasms.

Dr. Jan Abkowitz will present single cell transcriptomic and CITE-seq analyses of effective (normal) erythropoiesis and of the ineffective erythropoiesis seen in Diamond Blackfan anemia and MDS-5q. Most erythropoiesis takes place within erythroblastic islands (EBIs) comprised of a central macrophage (“nurse cell”) and 10-50 adjacent erythroid precursors. Dr. Abkowitz’s lab has recently isolated EBIs from human marrow and characterized their central macrophages at single cell resolution. She will describe how this cell normally functions as a safe and ecologically-efficient heme-iron recycler and how its dysfunction may contribute to MDS-5q anemia.

Dr. Radek Skoda will discuss the effects of iron availability on the phenotype of mouse models of myeloproliferative neoplasms (MPNs) driven by either JAK2-V617V or a N542-E543del mutation in JAK2 exon 12 (E12). While JAK2-V617F can manifest as polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis, expression of E12 results in PV, often with pure erythrocytosis phenotype. At baseline, PV patients with JAK2-V617V and JAK2-V617V mouse models with PV phenotype display iron deficiency, while ET patients and mice with an ET-like phenotype have normal iron stores. Dr. Skoda will describe the effects of iron deficiency and iron overload on the iron-responsive progenitor stages that decide between erythroid and megakaryocytic lineage choices and compare the effects of orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 on hemoglobin and iron parameters in JAK2-V617F and E12 mutant mouse models.

Co-Chairs:

Janis L. Abkowitz, MD
University of Washington
Seattle, WA

Radek C. Skoda, MD
Baylor College of Medicine
Houston, TX

Speakers:

Janis L. Abkowitz, MD
University of Washington
Seattle, WA
Role of Heme and Iron in Effective and Ineffective Erythropoiesis

Radek C. Skoda, MD
Baylor College of Medicine
Houston, TX
Impact of Iron Availability on Megakaryopoiesis

Phylogenetic Reconstruction of Hematopoiesis

Monday, December 9, 2024, 10:30 a.m. - 11:45 a.m.
San Diego Convention Center, Room 7

Hematopoiesis is a complex and highly regulated process that has been increasingly understood through advances in genetics, epigenetics, and single-cell genomics technologies. Recent work has focused on increasingly nuanced and detailed phylogenies of hematopoietic cells in normal and aged individuals, and multidimensional understanding of phylogenetic trees of stem cells, progenitors, and mature progeny. Genomics, epigenetics, advanced computational analyses, large scale datasets, and single-cell approaches are all integral in this effort. This session will present some of the latest advances in the field and serve to educate the audience of how these may inform our understanding of physiological and pathological mechanisms in hematopoiesis.

Co-Chairs:

Jyoti Nangalia, MBBChir PhD
Wellcome Sanger Institute
Hinxton, United Kingdom

Charles Gawad, MD
Stanford University
Memphis, TN

Speakers:

Jyoti Nangalia, MBBChir PhD
Wellcome Sanger Institute
Hinxton, United Kingdom
Incorporating Genetic and Epigenetic Marks in Phylogenetic Reconstruction of Blood Cells

Charles Gawad, MD
Stanford University
Memphis, TN
Novel Single-Cell Genomics Technologies to Reconstruct Phylogenetics of Human Blood Cells