62nd ASH Annual Meeting and Exposition: 603. Oncogenes and Tumor suppressors: Pre clinical models and Novel Targets

Oral and Poster Abstracts
Oral

Adult, AML, apoptosis, Biological, HSCs, Leukemia, Animal models, cell division, Diseases, cell regulation, Combinations, Therapies, MDS, Pediatric, Biological Processes, Technology and Procedures, Cell Lineage, Xenograft models, gene editing, Study Population, Clinically relevant, genetic profiling, genomics, Myeloid Malignancies, hematopoiesis, flow cytometry, inflammation, molecular interactions, RNA sequencing, pathogenesis, WGS, pathways, signal transduction

Moderators:

Kira Gritsman, MD, PhD, Albert Einstein College of Medicine and Camille Lobry, PhD, MSc, INSERM U944

Disclosures:

No relevant conflicts of interest to declare.

7:00 AM

518

ZRSR2 Mutation Induced Minor Intron Retention Drives MDS and Diverse Cancer Predisposition Via Aberrant Splicing of LZTR1

Daichi Inoue, MD, PhD^1,2, Jacob T. Polaski³^*, Justin Taylor, MD⁴, Pau Castel⁵^*, Sisi Chen¹^*, Susumu Kobayashi⁶^*, Simon J. Hogg, PhD, BSc¹^*, Yasutaka Hayashi⁷^*, Jose Mario Bello Pineda^3,8^*, Alexander V Penson, PhD¹^*, Ettaib El Marabti⁹^*, Caroline Erickson¹⁰^*, Miki Fukumoto⁷^*, Hiromi Yamazaki, PhD⁷^*, Chie Fukui⁷^*, Sydney X. Lu, MD, PhD¹¹, Benjamin H. Durham¹^*, Bo Liu, PhD¹^*, Sanjoy Mehta¹²^*, Daniel Zakheim¹²^*, Ralph Garippa, PhD¹³^*, Guo-Liang Chew¹⁴^*, Frank McCormick, PhD¹⁵^*, Robert K. Bradley, PhD^16,17^* and Omar Abdel-Wahab, MD ¹

¹Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY
²Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, HYO, Japan
³Public Health Sciences and Basic Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle
⁴Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Miami, FL
⁵Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco
⁶Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan
⁷Department of Hematology-Oncology, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan
⁸Department of Genome Sciences, University of Washington, Seattle
⁹Memorial Sloan Kettering Cancer Center, New York
¹⁰Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York
¹¹Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
¹²Gene Editing & Screening Facility, Memorial Sloan Kettering Cancer Center, New York
¹³Memorial Sloan Kettering Cancer Center, New York, NY
¹⁴Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
¹⁵UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
¹⁶Computational Biology Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
¹⁷Genome Sciences, University of Washington, Seattle, WA

7:15 AM

519

A Human Model of Down Syndrome Associated Leukemia Reveals Different Cell of Origins for Initiation and Progression

Elvin Wagenblast, PhD¹, Joana Araújo, MD²^*, Olga I. Gan, PhD³^*, Sarah K Cutting²^*, Alex Murison³^*, Jessica L. McLeod³^*, Gabriela Krivdova, BSc⁴, Maria Azkanaz²^*, Sabrina A Smith²^*, Johann K Hitzler, MD⁵, John E. Dick, PhD, FRS^3,6 and Eric R Lechman, Ph.D.²^*

¹Princess Margaret Cancer Centre, University Health Network (UHN), East York, ON, Canada
²Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
³Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, ON, Canada
⁴Princess Margaret Cancer Centre, University Health Network, Mississauga, ON, Canada
⁵The Hospital for Sick Children, Toronto, ON, Canada
⁶Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

7:30 AM

520

Using an in-Vivo Degron-Based Approach to Interrogate Dependencies of Serially Acquired Mutations - Including DNMT3a-R882 and NPM1c - in Acute Myeloid Leukemia

Andrew A Guirguis, MD, PhD^1,2,3, Alexander Tepper²^*, Max Jan, MD, PhD^2,4, Quinlan Sievers, MD, PhD² and Benjamin L. Ebert, MD, PhD^5,6,7

¹Dana-Farber Cancer Institute, Boston, MA
²Broad Institute of Harvard and MIT, Cambridge, MA
³Cancer Epigenetics, Peter MacCallum Cancer Institute, Melbourne, Australia
⁴Department of Pathology, Massachusetts General Hospital, Boston, MA
⁵Division of Hematology, Harvard Medical School, Boston, MA
⁶Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
⁷Broad Institute of MIT and Harvard, Cambridge, MA

7:45 AM

521

Male-Biased Spliceosome Mutations in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Impair pDC Activation and Apoptosis

Katsuhiro Togami, MD, PhD¹, Sun Sook Chung, PhD¹^*, Vikas Madan, PhD²^*, Christopher M. Kenyon, BS¹^*, Lucia Cabal-Hierro, PhD¹^*, Justin Taylor, MD³, Sunhee Kim, MD¹^*, Gabriel K Griffin, MD⁴^*, Mahmoud Ghandi⁵^*, Jia Li, PhD²^*, Yvonne Y. Li, PhD¹^*, Fanny Angelot-Delletre, PhD^6,7^*, Sabeha Biichle^6,7^*, Michael Seiler⁸^*, Silvia Buonamici, PhD⁸, Scott B Lovitch, MD, PhD⁴, Abner Louissaint Jr., MD, PhD⁹, Elizabeth A Morgan, MD⁴, Fabrice Jardin, MD, PhD¹⁰^*, Pier Paolo Piccaluga, MD, PhD^11,12,13^*, David M. Weinstock, MD^1,5, Peter S. Hammerman, MD, PhD¹^*, Henry Yang, PhD²^*, Marina Konopleva, MD, PhD¹⁴, Naveen Pemmaraju, MD¹⁴, Francine Garnache-Ottou, PhD^6,7^*, Omar Abdel-Wahab, MD ¹⁵, H. Phillip Koeffler, MD^2,16 and Andrew A Lane, MD, PhD^1,5

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
²Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
³Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, Miami, FL
⁴Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
⁵Broad Institute of Harvard and MIT, Cambridge, MA
⁶Univ. Bourgogne Franche-Comté, INSERM, EFS Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur - Ingénierie Cellulaire et Génique, LabEX LipSTIC, Besançon, France
⁷EFS Bourgogne Franche-Comté, Laboratoire d'Hématologie, Besançon, France
⁸H3 Biomedicine, Cambridge, MA
⁹Department of Pathology, Massachusetts General Hospital, Boston, MA
¹⁰Inserm U1245, Centre Henri Becquerel, Université de Rouen, IRIB, Rouen, France
¹¹Department of Experimental, Diagnostic, and Specialty Medicine, Bologna University Medical School, Bologna, Italy
¹²Department of Biomolecular Strategies, Genetics, Avant-Garde Therapies and Neurosciences (SBGN), Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy
¹³School of Health, Department of Pathology, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
¹⁴University of Texas, MD Anderson Cancer Center, Houston, TX
¹⁵Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY
¹⁶Cedars-Sinai Medical Center, Division of Hematology/Oncology, UCLA School of Medicine, Los Angeles, CA

8:00 AM

522

A Synthetic Lethal Approach to Eradicate AML Via Synergistic Activation of Pro-Apoptotic p53 By MDM2 and BET Inhibitors

Sha Li¹^*, Anne-Louise Latif²^*, Ashley Newcombe²^*, Kathryn Gilrory²^*, Neil Robertson²^*, Xue Lei¹^*, Darren Finlay³^*, Karina Barbosa, BSc¹, Helen Stewart⁴^*, John Cole²^*, Maria Terradas Terradas²^*, Loveena Rishi Delori²^*, Lynn McGarry⁵^*, Claire McKeeve⁶^*, Claire Reid²^*, William Clark⁵^*, Joana Campos²^*, Kristina Kirschner²^*, Andrew Davis¹^*, Jonathan Lopez²^*, Jun-Ichi Sakamaki⁵^*, Jennifer Morton²^*, Kevin Ryan⁵^*, Stephen Tait²^*, Sheela Abraham⁷^*, Tessa L. Holyoake, MD, PhD, FRCP, FRCPath², Brian Higgins⁸^*, Xu Huang, BSc, PhD²^*, Karen Blyth²^*, Mhairi Copland, PhD, MBBChir, FRCP, FRCPath², Timothy Chevassut⁴^*, Aniruddha J. Deshpande, PhD¹, Karen Keeshan²^* and Peter Adams, PhD¹^*

¹Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
²University of Glasgow, Glasgow, United Kingdom
³Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA
⁴University of Sussex, Brighton, United Kingdom
⁵Cancer Research UK Beatson Institute, Glasgow, United Kingdom
⁶Queen Elizabeth University Hospital, Glasgow, United Kingdom
⁷Queen's University, Ontario, Canada
⁸Roche Innovation Center, New York

8:15 AM

523

Transcriptional Control of HP1a By the RNA Binding Proteins Rbmx/L1 Maintain Chromatin State in Myeloid Leukemia

Diu T.T. Nguyen, DPhil¹, Camila Prieto, PhD¹^*, Zhaoqi Liu, PhD²^*, Justin Wheat³^*, Alexendar Perez¹^*, Saroj Gourkanti, BA¹^*, Timothy Chou, BS⁴^*, Ersilia Barin¹^*, Arthur Chow, BS¹^*, James Taggart, BA¹^*, Katerina Hoskova⁵^*, Meera Dhodapkar⁵^*, Alexandra Schurer, BS¹^*, Trevor Stephen Barlowe, BA⁶, Ly Vu, PhD^7,8, Christina Leslie, PhD⁹^*, Ulrich G. Steidl, MD/PhD¹⁰, Raul Rabadan, PhD²^* and Michael G. Kharas, PhD¹¹

¹Memorial Sloan Kettering Cancer Center, New York, NY
²Department of Systems Biology, Columbia University, New York, NY
³Albert Einstein College of Medicine, New York
⁴Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY
⁵University of Chicago, Chicago
⁶Dartmouth Geisel School of Medicine, Hanover, NH
⁷Simon Fraser University, Vancouver, BC, Canada
⁸BC cancer agency, vancouver, BC, Canada
⁹Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY
¹⁰Hematology/Oncology, Albert Einstein College of Medicine, Bronx, NY
¹¹Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY

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^*signifies non-member of ASH

603.O1.6 603. Oncogenes and Tumor suppressors: Pre clinical models and Novel Targets