66th ASH Annual Meeting: 503. Clonal Hematopoiesis, Aging, and Inflammation: Mechanisms of Hematopoietic Aging and Inflammation

Symposia: Clonal Hematopoiesis, Aging, and Inflammation Oral and Poster Abstracts
Oral

Research, Fundamental Science, Acquired Marrow Failure Syndromes, CHIP, Translational Research, Bone Marrow Failure Syndromes, Genetic Disorders, Hematopoiesis, Immune mechanism, Diseases, Immune Disorders, Immunology, Metabolism, Biological Processes, Myeloid Malignancies, Molecular biology, Multi-systemic interactions, Pathogenesis

Grand Hall D (Manchester Grand Hyatt San Diego)

Moderators:

Gregor Hoermann, MD, PhD, MLL Munich Leukemia Laboratory and Lambert Busque, MD, Maisonneuve-Rosemont Hospital

Disclosures:

Hoermann: Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Cogent: Membership on an entity's Board of Directors or advisory committees. Busque: Novartis: Consultancy, Honoraria; GSK: Consultancy.

2:00 PM

187

The Mechanism of Cell Autonomous Inflammation in VEXAS Syndrome Is Mediated By Proteotoxic Stress

Samuel J Magaziner, MPhil¹, Jason C Collins, PhD²^*, Brecca Miller^1,3^*, Kelly V Ruggles, PhD³^*, Achim Werner, PhD²^* and David B Beck, MD, PhD¹^*

¹Center for Human Genetics and Genomics, NYU Grossman School of Medicine, New York, NY
²Stem Cell Biochemistry Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD
³Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY

2:15 PM

188

In Vivo barcoded CRISPR-Cas9 Screen Identifies Ncoa4-mediated Ferritinophagy As a Dependence in Tet2-Deficient Haemopoiesis

Justin CT Loke, MD PhD^1,2, Geon Kim, MD¹^*, Meaghan Boileau, PhD³^*, Thuy T.P. Nguyen, PhD⁴^*, Marie E McConkey, PhD¹^*, Aidan P. Miller, BSc¹^*, Wesley Shin¹^*, Christopher B. Hergott, MD, PhD^1,5^*, Maria Ericsson, PhD⁶^*, Anja E.H. Nordstrom⁶^*, Scott A Armstrong, MD, PhD³, Joseph D Mancias, MD PhD⁴^* and Benjamin Levine Ebert, MD, PhD^1,7,8

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
²University of Birmingham, Birmingham, United Kingdom
³Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
⁴Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA
⁵Department of Pathology, Brigham and Women’s Hospital, Boston, MA
⁶Department of Cell Biology, Harvard Medical School, Boston, MA
⁷Broad Institute of MIT and Harvard University, Cambridge, MA
⁸Howard Hughes Medical Institute, Boston, MA

2:30 PM

189

The High Mobility Group A1 (HMGA1) Chromatin Regulator Induces Inflammatory Signals and Promotes Atherogenesis in Tet2 Mutant Clonal Hematopoiesis

Zanshe Thompson, PhD, MS¹, Iliana Herrera, BS²^*, Zion Williams²^*, Li Z Luo, PhD³^*, Audrey-Ann Supreme, BS^4,5^*, Bailey West, BS⁶^*, Hyunsung Woo, MS⁷^*, Marios Arvantis, MD⁸^*, Charles Lowenstein⁹^*, Lewis Becker¹⁰^* and Linda Resar, MD¹¹

¹Division of Hematology, The Johns Hopkins University School of Medicine, Owings Mills, MD
²The Johns Hopkins University School of Medicine, Baltimore
³Department of Medicine, Division of Hematology, The Johns Hopkins University School of Medicine, Baltimore, MD
⁴Doctoral Diversity Program, Johns Hopkins University School of Medicine, Baltimore, MD
⁵Department of Medicine, Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD
⁶Pathobiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD
⁷The Johns Hopkins University, Baltimore
⁸Cardiology, The Johns Hopkins University School of Medicine, Baltimore
⁹The Johns Hopkins University School of Medicine, Baltimore, MD
¹⁰Johns Hopkins University School of Medicine, Baltimore, MD
¹¹Division of Hematology, Departments of Medicine, Oncology & Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD

2:45 PM

190

Delayed Trp53 Activation Protects Dnmt3a-Mutant Haematopoietic Stem Cells from Inflammatory Attrition

Ludovica Marando, MD, PhD¹, George Giotopoulos, PhD²^*, Pedro Madrigal³^*, Dhoyazan M A Azazi³^*, Ryan Asby³^*, Maria Erendira Calleja-Cervantes⁴^*, David Lara-Astiaso³^*, Nicola K. Wilson⁵^*, Rebecca Hannah⁵^*, Jaana Bagri³^*, Elsa Barnard⁶^*, Sarah J Horton, PhD²^*, Berthold Gottgens³, Elli Papaemmanuil⁷, Shuchi Agrawal Singh³^*, Malgorzata Gozdecka³^*, George S Vassiliou, MD, PhD³ and Brian J P Huntly, MD³^*

¹University of Cambridge, Cambridge, United Kingdom
²Cambridge Stem Cell Institute, Cambridge, United Kingdom
³Department of Haematology and Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
⁴Centro de Investigación Médica Aplicada, University of Navarra, Pamplona, Spain
⁵Department of Hematology, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
⁶Memorial Sloan Kettering Cancer Center, New York, NY
⁷Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY

3:00 PM

191

Hematopoietic Stem Cell Aging Promotes Expansion of Tet2 Mutant Clones By Cell Intrinsic Mechanisms

Marco De Dominici, PhD^1,2, Lamis Naddaf, PhD³, Vadym Zaberezhnyy⁴^*, Andrew Goodspeed⁴^*, Sheng Li, PhD⁵^* and James Degregori, PhD⁶

¹University of Colorado, Aurora, CO
²University of Colorado Anschuz Medical Campus, Aurora, CO
³USC Keck School of Medicine - University of Southern California, Farmington, CT
⁴University of Colorado Anschutz Medical Campus, Aurora, CO
⁵Biochemistry and Molecular Medicine, University of Southern California, Los Angeles, CA
⁶Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO

3:15 PM

192

Exploring the Mechanism of Chromatin Spatial Structure Changes and Transcriptional Regulation in Age-Related Clonal Hematopoiesis Caused By DNMT3A Mutations Using Chromatin Capture Technology

Yujun Dai, MD, PhD¹^*, Xue-Ping Li²^* and Yang Liang³

¹Sun Yat-sen University Cancer Center (SYSUCC), Shanghai, China
²Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
³Department of Hematological Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China

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^*signifies non-member of ASH

503.O2.6 503. Clonal Hematopoiesis, Aging, and Inflammation: Mechanisms of Hematopoietic Aging and Inflammation