66th ASH Annual Meeting: 503. Clonal Hematopoiesis, Aging, and Inflammation: Poster I

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

Research, Fundamental Science, Lymphoid Leukemias, Acute Myeloid Malignancies, AML, Adult, Translational Research, CHIP, Bone Marrow Failure Syndromes, CLL, Assays, Elderly, Clinical Research, Genomics, Bioinformatics, Hematopoiesis, GVHD, Immune mechanism, Diseases, Immune Disorders, SARS-CoV-2/COVID-19, Infectious Diseases, Immunology, Lymphoid Malignancies, Metabolism, Young adult , Biological Processes, Myeloid Malignancies, Technology and Procedures, Molecular biology, Multi-systemic interactions, Study Population, Profiling, Human, Pathogenesis, Animal model, Machine learning, Omics technologies

Halls G-H (San Diego Convention Center)

1282

A Senescent Subset in Human Hematopoietic Stem Cell (HSC) Compartment As Target for Senotherapy

Laura Poisa-Beiro, PhD¹^*, Jonathan JM Landry, PhD²^*, Bowen Yan, PhD³^*, Michael Kardorff¹^*, Volker Eckstein, PhD¹^*, Laura Villacorta⁴^*, Anne-Claude Gavin, PhD⁵^*, Judith Zaugg, PhD⁶^*, Vladimir Benes⁷^*, Simon Raffel, MD¹^*, Daohong Zhou, MD⁸^* and Anthony D Ho, MD¹

¹Department of Medicine V, Universität Heidelberg, Heidelberg, Germany
²EMBL, Heidelberg, BW, DEU
³University of Florida, Gainesville, FL
⁴Genomic Core Facility, European Molecular Biology Laboratories, Heidelberg, Heidelberg, Germany
⁵Department for Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
⁶European Molecular Biology Laboratories, Heidelberg, Germany
⁷Genomic Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany
⁸Department of Biochemistry and Structural Biology and Center for Innovative Drug Discovery, University of Texas Health Science Center at San Antonio, San Antonio, TX

1283

Statin Therapy Is Associated with Reduced Clonal Expansion in TET2 Mutated Clonal Haematopoiesis of Indeterminate Potential

Ellen Nuttall Musson¹^*, Yvette Hoade, BSc²^*, Phoebe Dace, BSc³^*, Helen Brown, PhD²^*, Madison Hill, Biomed (hons)²^*, Alexandra Lubin, PhD², Katie-Jo Miller, BSc²^*, Catherine Zhu, FRCPath, MA, MBBChir²^*, Javier Herrero, PhD²^*, Andrew Steptoe, DPhil, DSc, FBA, FMedSci, FRSB⁴^*, Spiros Denaxas, PhD^5,6^* and Elspeth Payne, MD, PhD, FRCPath^2,7

¹UCL Cancer Institute, University College London, London, ENG, United Kingdom
²UCL Cancer Institute, University College London, London, United Kingdom
³The Francis Crick Institute, London, United Kingdom
⁴Institute of Epidemiology and Health Care, University College London, London, United Kingdom
⁵Institute of Health Informatics, University College London, London, United Kingdom
⁶British Heart Foundation Data Science Centre, London, United Kingdom
⁷University College London Hospitals NHS Foundation Trust, London, United Kingdom

1284

DNMT3A-Mutant Clonal Haematopoiesis Is Associated with Worse Recovery after ST-Elevation Myocardial Infarction Via Increased Inflammation

Sarah J Mackie¹^*, Matthew Sadler²^*, Maroof Hasan³^*, Lynette Graver⁴^*, Rupavidhya Mondi Anandhakrishna⁵^*, Fulye Argunhan⁵^*, Louis-Francois Handfield¹^*, Hosanna Assefa-Kebede⁶^*, Laarni Bogaanay⁷^*, Prodromos Chatzikyriakou, Ph.D.⁸^*, Pilar Casares Alaez⁹^*, Antonio Cannata⁵^*, Mohammad Al-Agil¹⁰^*, Amandine Tan¹^*, Maria Ortiz Estevez¹¹^*, Ching-Pin Chang¹²^*, Rajasekhar N.V.S. Suragani, PhD¹³, Anita K. Gandhi, PhD¹⁴, Ajay Shah¹⁵^*, Theresa McDonagh¹⁶^*, Aleksander Ivetic¹⁶^*, Ghulam Mufti¹^*, Giorgio Napolitani, PhD¹^*, Daniel Bromage²^* and Lynn Quek, MD, Ph.D.⁸^*

¹Comprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
²British Heart Foundation Centre, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, United Kingdom
³Hematology, Translational Medicine and Disease Team, Bristol Myers Squibb, Summit, NJ
⁴Comprehensive Cancer Centre, School of Cancer and Pharmaceutical Sciences, King's College London, london, United Kingdom
⁵School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, london, United Kingdom
⁶Department of Cardiology, King's College Hospital London, London, United Kingdom
⁷School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
⁸Myeloid Leukaemia Genomics and Biology Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
⁹Myeloid Leukaemia Genomics and Biology Group, School of Cancer and Pharmaceutical Sciences, King’s College London, London, United Kingdom
¹⁰CogStack Department, King's College Hospital London, London, United Kingdom
¹¹Bristol Myers Squibb, Sevilla, Spain
¹²Bristol Myers Squibb, Princeton, NJ
¹³Hematology Translational Medicine, Bristol Myers Squibb, Cambridge, MA
¹⁴Hematology, Translational Medicine, Bristol Myers Squibb, Summit, NJ
¹⁵School of Cardiovascular and Metabolic Medicine & Sciences, King's College Hospital London, London, United Kingdom
¹⁶School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, United Kingdom

1285

Predictive Modeling of Clonal Hematopoiesis across Diverse Cohorts

Armel L. Batchi-Bouyou, MD, MPH¹^*, Duc Tran, PhD¹^*, Michael Raddatz, MD, PhD²^*, Teng Gao, PhD³^*, Caitlyn Vlasschaert, MD, PhD⁴^*, Brian Sharber, MS⁵^*, Jie Liu, MBBS, PhD¹, Giulia Petrone, MD, MBBS⁶, Irenaeus C.C. Chan, MSc¹^*, J. Scott Beeler, MD, PhD¹^*, Griffen Mustion, MS¹^*, Sean M. Devlin, PhD⁷^*, Alexander G. Bick, MD, PhD⁵^* and Kelly Bolton, MD, PhD⁸

¹Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
²Department of Medicine, University of California, Los Angeles, Los Angeles, CA
³Department of Biomedical Informatics, Harvard University, Cambridge, MA
⁴Department of Medicine, Queen’s University, Kingston, ON, Canada
⁵Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN
⁶Washington University, Saint Louis, MO
⁷Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY
⁸Washington University School of Medicine, St Louis, MO

1286

Endothelial Protein C Receptor CD201 Enables Identification of Transplantable Mouse Hematopoietic Stem Cells in Inflammatory Conditions Unlike SCA1

Kavita Bisht, PhD¹, Svetlana Shatunova¹^*, Valerie Barbier¹^*, Ingrid G Winkler²^* and Jean-Pierre Levesque, PhD¹^*

¹Mater Research Institute-The University of Queensland, Woolloongabba, QLD, Australia
²Mater Research Institutee - The University of Queensland, Brisbane, AUS

1287

Inflammatory Reprogramming of the Tumor Microenvironment By Clonal Hematopoiesis Is Associated with Clinical Outcomes in Solid Cancer

Marco M Buttigieg, MSc¹^*, Caitlyn Vlasschaert, MD, PhD²^*, Robert J Vanner, MD, PhD^3,4 and Michael J. Rauh, MD, PhD¹

¹Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
²Department of Medicine, Queen’s University, Kingston, ON, Canada
³Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
⁴Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada

1288

Dnmt3a Mutant Hematopoietic Stem Cells Produce Hyperactive T Cells with Increased Alloimmune and Anti-Leukemic Activity

LaShanale Wallace, PhD¹, Mark Engelken¹^*, Jacquelyn A. Myers¹^*, John Harper¹^*, Brandi Clark, PhD²^*, David Cullins³^*, Jaquelyn T. Zoine, PhD⁴, Raghuvaran Shanmugam²^*, Stefan Schattgen, PhD²^*, Mireya Paulina Velasquez, MD⁴, Heather Sheppard, DVM, PhD⁵^*, Jeremy Chase Crawford, PhD²^*, Paul G. Thomas, PhD²^* and Esther A. Obeng, MD, PhD⁶

¹Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN
²Department of Host Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN
³Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN
⁴Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN
⁵Comparative Pathology Core, St Jude Children's Research Hospital, Memphis, TN
⁶St. Jude Children's Research Hospital, Memphis, TN

1289

Emergence of DNA Damage Repair Clonal Hematopoiesis after Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors

Romain Loyaux¹^*, Julien Hadoux²^*, Sandrine Oziel³^*, Alice Durand⁴^*, Karine Bouhier-Leporrier⁵^*, Lavinia Vija⁶^*, Magalie Haissaguerre⁷^*, Aurelie Ferru⁸^*, Livia Lamartina²^*, Desiree Déandreis²^*, Laura Gerard⁴^*, Arnaud Pages, MD; PhD⁹^*, Rachel El-Ferkh²^*, Amira Habza²^*, Galina Jepiral²^*, Michel Ducreux¹⁰^*, Christophe Marzac, MD¹¹^*, Thomas Walter⁴^*, Nathalie Charrier³^*, Noémie Simon-Tillaux²^*, Eric Baudin¹²^* and Jean-Baptiste Micol, MD¹³

¹Gustave Roussy, VILLEJUIF, France
²Gustave Roussy, Villejuif, France
³INSTITUT PAOLI CALMETTES, Marseille, France
⁴CHU LYON, LYON, France
⁵CHU CAEN, CAEN, France
⁶IUCT Oncopole, TOULOUSE, France
⁷CHU BORDEAUX, BORDEAUX, France
⁸CHU POITIERS, POITIERS, France
⁹Gustave Roussy Institute, Villejuif, France
¹⁰Institut Gustave Roussy, Villejuif, FRA
¹¹Institut Gustave Roussy, Villejuif, France
¹²Gustave Roussy, Service De MéDecine NucléAire, Villejuif, FRA
¹³Hematology Department, Gustave Roussy Institute, Villejuif, France

1290

Mitochondrial Potentiation Screen in Aged Hematopoietic Stem Cells Identified Known and Novel Rejuvenation Drugs

Stephan Emmrich, PhD¹ and Nicola Vannini²^*

¹Department of Oncology, University of Lausanne, Epalinges, Switzerland
²University of Lausanne, Epalinges, Switzerland

1291

The Effect of TET2 Loss on Macrophage Phagocytosis

Aidan Patrick Miller¹^*, Wesley Shin¹^*, Marie E McConkey, PhD¹^*, Justin CT Loke, MD PhD^1,2, Geon Kim, MD¹ and Benjamin L. Ebert, MD, PhD^1,3,4

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
²University of Birmingham, Birmingham, United Kingdom
³Broad Institute of MIT and Harvard, Cambridge, MA
⁴Howard Hughes Medical Institute, Boston, MA

1292

Mapping Genotype to Phenotype in Clonal Hematopoiesis Uncovers Downregulated MHC-II Molecules in DNMT3A^R882- Mutant Hematopoietic Stem Cells

Patrick Stelmach, MD¹^*, Dominik Vonficht, PhD²^*, Anne Kathrin Merbach, PhD³^*, Dawn S Lin, PhD¹^*, Sergi Beneyto-Calabuig, PhD⁴^*, Marina Scheller, PhD⁵^*, Aino-Maija Leppä, PhD¹^*, Florian Grünschläger, PhD²^*, George S Vassiliou, MD, PhD⁶, Simon Haas, PhD^7,8^*, Lars Velten, PhD⁴^*, Carsten Müller-Tidow, MD^9,10^* and Andreas Trumpp, PhD^1,11

¹Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
²Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, DEU
³Department of Medicine V, Heidelberg University Hospital, Heidelberg, Germany
⁴The Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), Barcelona, ESP
⁵Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany
⁶Department of Haematology and Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
⁷Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany
⁸Berlin Institute for Medical Systems Biology, MDC for Molecular Medicine in the Helmholtz Association, Berlin, Germany
⁹Department of Medicine V, Heidelberg University Hosptial, Heidelberg, Germany
¹⁰Molecular Medicine Partnership Unit (MMPU), European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
¹¹Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany

1293

iPSC Reprogramming Identifies the Role of Cryptic Drivers in Preleukemic Clonal Evolution

Martina Sarchi, MD, PhD^1,2^*, Sintra Stewart²^*, Jason Kim²^*, Ksenia R. Safina, PhD³^*, Stephanie Busch²^*, Hayden Gizinski²^*, Nelli Aydinyan²^*, Andreea Reilly, PhD²^*, J. Philip Creamer IV, PhD², Rochelle Bergantinos²^*, Jasper Hsu²^*, Jonathan Good³^*, Malgorzata Olszewska^4,5^*, Anna Gallì⁶^*, Luca Malcovati, MD^6,7, Sioban Keel, MD², David Wu, MD, PhD⁸^*, Janis L. Abkowitz, MD^2,9, Pamela S. Becker, MD, PhD^10,11, Eirini Papapetrou, MD, PhD^4,5, Kelley Harris, PhD^9,12^*, Peter van Galen, PhD^3,13,14, Suleyman Gulsuner, MD, PhD¹⁵^* and Sergei Doulatov, PhD^2,9,16

¹Department of Molecular Medicine, University of Pavia, Pavia, Italy
²Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA
³Division of Hematology, Brigham and Women's Hospital, Boston, MA
⁴Department of Oncological Sciences and Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY
⁵Center for the Advancement of Blood Cancer Therapies, Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
⁶Department of Hematology, IRCCS S. Matteo Hospital Foundation, Pavia, Italy
⁷Department of Molecular Medicine, University of Pavia, Piazzale Golgi 2, Italy
⁸Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA
⁹Department of Genome Sciences, University of Washington, Seattle, WA
¹⁰Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
¹¹Department of Hematologic Malignancies Translational Science, City of Hope Beckman Research Institute, Duarte, CA
¹²Herbold Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA
¹³Broad Institute of MIT and Harvard, Cambridge
¹⁴Ludwig Center at Harvard, Harvard Medical School, Boston, MA
¹⁵Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA
¹⁶Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA

1294

Patient-Derived Models of Clonal Hematopoiesis Point to Cell-Intrinsic and -Extrinsic Contributions to Clonal Dominance and Lineage Imbalances

Mareike Peters¹^*, Jiajun Xie, MD²^*, Sergiu Pasca³^*, Hamzah Kharabsheh²^*, Anna S Nam, MD⁴^*, Lukasz P. Gondek, MD, PhD⁵ and Gabriel Ghiaur, MD, PhD⁶

¹Johns Hopkins University, Baltimore, MD
²Johns Hopkins University, Baltimore
³Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
⁴Weill Cornell Medicine, New York
⁵Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
⁶Division of Hematologic Malignancies, Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center, John's Hopkins Hospital, Baltimore, MD

1295

Associations of Lineage-Specific Clonal Hematopoiesis with COVID-19 Hospitalization and Mortality

Yasmeen Choudhri, MSc, BSc¹^*, Olivia Lopes, MSc²^*, Caitlyn Vlasschaert, MD, PhD³^*, David M. Maslove, MD, MS^4,5^* and Michael J. Rauh, MD, PhD¹

¹Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
²Department of Medicine, University of Ottawa, Ottawa, ON, Canada
³Department of Medicine, Queen’s University, Kingston, ON, Canada
⁴Department of Medicine, Queen's University, Kingston, ON, Canada
⁵Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada

1296

Title: Clonal Hematopoiesis and Germline Predisposition in High-Risk Leukemia Pedigrees

Afaf Osman, MD¹, Julie Feusier, PhD²^*, Brian Avery, PhD³^*, Deborah M. Stephens, DO⁴, Michael Madsen, MStat⁵^*, Justin Williams, MPH⁵^*, Tony Pomicter, MS⁶^*, Brandt Jones, BS⁵^*, Adam Clayton⁷^*, Philippe Szankasi, PhD²^*, Jay Patel, MD⁸, Ramiro Garzon, MD⁹^* and Nicola J Camp, PhD¹⁰^*

¹Department of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, UT
²ARUP Laboratories, Salt Lake City, UT
³Huntsman Cancer Institute and School of Medicine, University of Utah, Salt Lake City, UT
⁴University of North Carolina Chapel Hill, Chapel Hill, NC
⁵Huntsman Cancer Institute, Salt Lake City, UT
⁶The University of Utah, Salt Lake City, UT
⁷ARUP laboratories, Salt Lake City
⁸University of Utah, ARUP Laboratories, Salt Lake City, UT
⁹Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah Health, Salt Lake City, UT
¹⁰Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

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^*signifies non-member of ASH

503.P1.47 503. Clonal Hematopoiesis, Aging, and Inflammation: Poster I