66th ASH Annual Meeting: 102. Iron Homeostasis and Biology: New Insights into Iron-related Proteins in Erythropoiesis and Inflammation

Symposia: Iron Homeostasis and Biology Oral and Poster Abstracts
Oral

Research, Fundamental Science, Iron Deficiency, Translational Research, Iron Overload, Drug development, Genetic Disorders, Thalassemia, Hemoglobinopathies, Hematopoiesis, Diseases, Immune mechanism, Treatment Considerations, Metabolism, Biological Processes, Myeloid Malignancies, Metabolic Disorders, Molecular biology, Study Population, Animal model, Pathogenesis, Maternal Health

Room 29 (San Diego Convention Center)

Moderators:

Imo J. Akpan, MD, Columbia University and Laura Silvestri, PhD, San Raffaele Scientific Institute %26 Vita-Salute Uni.

Disclosures:

Akpan: Pharmacosmos Therapeutics Inc: Consultancy, Honoraria, Speakers Bureau. Silvestri: Novo Nordisk: Consultancy, Honoraria.

In this session we will explore the complex mechanisms that modulate erythropoiesis and inflammation, focusing on the emerging role of iron-related proteins. These include the unconventional function of the iron storage protein ferritin in regulating EPO receptor signaling, the new insights into the reciprocal regulation between inflammation and hepcidin-ferroportin function, the unexpected role of the RNA-binding protein RBM28 in the modulation of heme synthesis via ferrochelatase, the identification of a novel and promising drug for erythropoietic protoporphyria, and the effect of maternal iron overload on epigenetic changes in fetal brain.

9:30 AM

Erythroid Ferritin Chains In Vivo Are Dispensable for Hemoglobinization but Play a Critical Non-Canonical Role in Erythropoietin Signaling

Ranjit Sahu¹^*, Kurt Langberg¹^*, Lorrie Delehanty¹^*, Kamaleldin E Elagib¹^*, Deepika Kotay¹^*, James Zimring¹, Angelo D'Alessandro, PhD² and Adam Goldfarb¹^*

¹Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA
²Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO

9:45 AM

TMPRSS6 Antisense Oligonucleotide Therapy Reverses Inflammation in Jak2^V617F Mutant Mice

Maayan Levy¹^*, Huihui Li^2,3, Andrew Dunbar, MD^4,5, Zixing Huang^2,3^*, Young Park⁵^*, Min Lu⁶, Pinanong Na Phattalung¹^*, Marina Planoutene¹^*, Carla Casu⁷^*, Stefano Rivella, PhD⁷, Shuling Guo⁸^*, Ross L Levine, MD⁵, Ronald Hoffman, MD⁹ and Yelena Ginzburg, MD¹

¹Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
²Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
³Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
⁴Department of Hematopoietic Biology & Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
⁵Memorial Sloan Kettering Cancer Center, New York, NY
⁶The Tisch Cancer Institute, Division of Hematology & Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
⁷Children's Hospital of Philadelphia, Philadelphia, PA
⁸Ionis Pharmaceuticals, Inc, Carlsbad, CA
⁹Division of Hematology & Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

10:00 AM

Inflammation-Driven NFκB Signaling Represses Ferroportin Transcription in Macrophages Via HDAC 1 and 3

Oriana Marques¹^*, Natalie Horvat²^*, Laura Zechner³^*, Silvia Colucci²^*, Richard Sparla²^*, Stefan Zimmermann²^*, Christopher Neufeldt²^*, Sandro Altamura²^*, Qiu Ruiyue³^*, Katja Müdder³^*, Guenter Weiss⁴^*, Matthias Hentze⁵^* and Martina U. Muckenthaler⁶

¹Universitatsklinikum Heidelberg, Heidelberg, DEU
²University of Heidelberg, Heidelberg, DEU
³University of Heidelberg, Heidelberg, Germany
⁴Medical University of Innsbruck, Innsbruck, AUT
⁵European Molecular Biology Laboratory, Heidelberg, Germany
⁶University of Heidelberg, Heidelberg, Baden-Württemberg, Germany

10:15 AM

In a Mouse Model of β-Thalassemia Intermedia Pregnancy, Maternal Iron Overload and Anemia Adversely Impact Fetal Development Regardless of Fetal Genotype

Lucia Lee¹^*, Vida Zhang, PhD¹^*, Veena Sangkhae, PhD¹, Yue He²^*, Jacob Shine²^*, Tomas Ganz, MD, PhD³, James F Collins²^* and Elizabeta Nemeth, PhD³

¹Center for Iron Disorders, David Geffen School of Medicine at UCLA, Los Angeles, CA
²University of Florida, Gainesville, FL
³Center for Iron Disorders, University of California, Los Angeles, Los Angeles, CA

10:30 AM

PORT-77, a Novel and Potent Inhibitor of ABCG2, Protects Against Skin Photo Toxicity and Liver Damage in a Mouse Model of Erythropoietic Protoporphyria (EPP)

Bhavik Shah, PhD¹^*, Edmond Huang, PhD²^*, Yvonne Pak²^*, Chris Henry²^*, Sunita Babbar²^*, Athiwat Hutchaleelaha²^*, Robert Zamboni²^*, Xiaochao Ma³^*, Pete Schmidt²^*, Morgan Paull²^* and Uma Sinha, PhD²

¹BridgeBio Pharma, winchester, MA
²BridgeBio Pharma, Palo Alto, CA
³University of Pittsburgh, Pittsburgh, PA

10:45 AM

Rbm38 Regulates Heme Biosynthesis Via Fine-Tuning the RNA Alternative Splicing, Stability and Translation of Porphyrin Metabolic Enzyme Gene Ferrochelatase (Fech)

Xinshu Xie¹^*, Ailin Zou¹^*, Kang Liu²^*, Lu Liu, PhD³ and Yang Mei, PhD¹^*

¹The affiliated Xiangtan Central Hospital of Hunan University, Hunan Provincial Key Laboratory of Animal Model and Molecular Medicine, School of Biomedical Sciences, Hunan University, Changsha, China
²The affiliated Xiangtan Central Hospital of Hunan University, Changsha, China
³School of Biomedical Sciences, Hunan University, Changsha, China

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^*signifies non-member of ASH

102.O1.6 102. Iron Homeostasis and Biology: New Insights into Iron-related Proteins in Erythropoiesis and Inflammation