66th ASH Annual Meeting: 602. Myeloid Oncogenesis: Basic: CRISPR Screens and Other New Approaches to Understanding Myeloid Neoplasia

Symposia: Myeloid Oncogenesis: Basic Oral and Poster Abstracts
Oral

Research, Fundamental Science, Acute Myeloid Malignancies, AML, Apoptosis, Assays, Translational Research, Drug development, Genomics, Bioinformatics, CML, Hematopoiesis, Chronic Myeloid Malignancies, Diseases, Immunology, Treatment Considerations, Computational biology, Myeloid Malignancies, Biological Processes, Molecular biology, Technology and Procedures, Gene editing, Profiling, Pathogenesis, Omics technologies

Seaport Ballroom ABCD (Manchester Grand Hyatt San Diego)

Moderators:

Kentson Lam, MD, PhD, University of California, San Diego and Dang Hai Nguyen, PhD, University of Minnesota

Disclosures:

No relevant conflicts of interest to declare.

These studies use various functional genetics approach to identify novel vulnerabilities of AML cells.

4:30 PM

949

CRISPR/Cas9 Library Screens Identified Atp2a2 As an In Vivo Specific Tumor Suppressor in Myeloid Neoplasms

Ruka Shimura, MSc¹^*, Moe Tamura, PhD²^*, Keita Yamamoto, MD, PhD²^*, Kohei Iida, PhD²^*, Shuhei Asada, MD, PhD³, Emi Sugimoto, PhD²^*, E. Christine Pietsch, PhD⁴, Barbara A. Weir⁴^*, Ramona Crescenzo, PhD⁵^*, Glenn S. Cowley⁴^*, Ricardo M. Attar, PhD⁶^*, Ulrike Philippar, PhD⁷, Satoshi Yamasaki, PhD⁸^*, Taisei Hirouchi, PhD⁹^*, Kaoru Uchimaru, MD, PhD⁹^*, Toshio Kitamura, MD, PhD^10,11 and Susumu Goyama, MD, PhD²^*

¹Graduate School of Frontier Sciences, The University of Tokyo, Minato-Ku, Japan
²Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
³The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
⁴Janssen Research and Development, Spring House, PA
⁵Janssen Research and Development, Beerse, Belgium
⁶Janssen Research & Development, Spring House, PA
⁷Janssen Research & Development, Beerse, Belgium
⁸Institute of Medical Science, University of Tokyo, Tokyo, Japan
⁹Laboratory of Tumor Cell Biology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
¹⁰Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
¹¹Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan

4:45 PM

950

Systematic Evaluation of GAPs and Gefs Identifies ARHGAP45 As a Targetable Leukemia-Specific Dependency

Pu Zhang¹^*, Zhendong Cao¹^*, Xiangyu Pan¹^*, Yuqiao Liu²^*, Cynthia Castro¹^*, Won Jun Kim¹^*, Takeshi Fujino³^*, Jennifer Lewis¹^*, Jahan Rahman⁴^*, Sanam Shahid, MD⁵, Jasmine S. Um³^*, Erin R. Burns³^*, Bing-Yi Chen³^*, Winson Cai³^*, Juliana Ortiz-Pacheco¹^*, Zhuoning Li¹^*, Mara Monetti¹^*, Anthony F. Daniyan, MD⁶^*, Christopher R. Vakoc, MD, PhD⁷^*, Omar Abdel-Wahab, MD⁸ and Junwei Shi, PhD⁹^*

¹Memorial Sloan Kettering Cancer Center, New York
²University of Pennsylvania, Philadelphia
³Memorial Sloan Kettering Cancer Center, New York, NY
⁴Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, NY
⁵Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY
⁶Department of Medicine, Cell Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY
⁷Cold Springs Harbor Laboratory, Cold Spring Harbor, NY
⁸Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
⁹Department of Cancer Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA

5:00 PM

951

CRISPR/RfxCas13d Screening Identifies the Long Non-Coding RNA (LncRNA) Nfyc-AS1 As a Molecular Vulnerability in Acute Myeloid Leukemia (AML)

Dimitrios Papaioannou, MD¹, Giovanni Gambi, PhD²^*, Palaniraja Thandapani, PhD³^*, Deedra Nicolet, MS⁴^*, Ziyan Lin⁵^*, Krzysztof Mrózek, MD, PhD⁴, Olha Ivashkiv²^*, Maria Sirenko, PhD⁶, Bettina Nadorp, PhD⁷^*, Ann-Kathrin Eisfeld, MD^4,8, Aristotelis Tsirigos, PhD^2,5^* and Iannis Aifantis, PhD⁶

¹Department of Medicine, Division of Hematology/Oncology, NYU Grossman School of Medicine, New York, NY, New York, NY
²Department of Pathology, New York University Grossman School of Medicine, New York, NY
³MD Anderson Cancer Center, Houston
⁴The Ohio State University Comprehensive Cancer Center, Columbus, OH
⁵Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY
⁶Department of Pathology, NYU Grossman School of Medicine, New York, NY
⁷NYU Grossman School of Medicine, Division of Precision Medicine, Department of Medicine, New York, NY
⁸Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH

5:15 PM

952

Identification of a Novel Chromatin Structure Associated with the Transcriptional Response to Menin Inhibitors in AML

Pablo R Freire, PhD¹^*, Brandon Regalado²^*, Elizabeth Ener³^*, Jevon Cutler, PhD², Christian Marinaccio, PhD²^*, Vassilena Sharlandjieva⁴^*, Thomas A Milne⁴ and Scott A Armstrong, MD, PhD^2,5

¹Department of Pediatric Oncology, Dana-Farber Cancer Institute, Jamaica Plain, MA
²Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
³Stanford University, Palo Alto, CA
⁴Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
⁵Boston Children's Hospital, Boston

5:30 PM

953

Targeted Protein Degradation Reveals a Repressive Role of Mecom at the CEBPA Locus to Prevent Differentiation in High-Risk Acute Myeloid Leukemia

Travis Fleming, BS^1,2,3^*, Richard A Voit, MD, PhD^2,3,4,5^*, Mateusz Antoszewski, PhD^1,2,3^*, Sander Lambo, PhD^2,3,4^*, Michael Gundry, MD, PhD^2,3,4^*, Riccardo Piussi^2,3,4^*, Sanjana Shah^2,3,4, Lara Wahlster, MD, PhD^2,3,4, Andrea Arruda⁶^*, Volker Hovestadt, PhD^2,3,4^*, Mark D. Minden, MD, PhD^6,7^* and Vijay G. Sankaran, MD, PhD^2,3,4

¹Division of Hematology/Oncology, Boston Children’s Hospital, Harvard Medical School, Boston, MA
²Division of Pediatric Oncology, Dana-Farber Cancer Institute / Harvard Medical School, Boston, MA
³Broad Institute of MIT and Harvard, Cambridge, MA
⁴Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA
⁵Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX
⁶Princess Margaret Cancer Centre / University Health Network, Toronto, ON, Canada
⁷Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

5:45 PM

954

A Protein-Coding Circular RNA That Regulates DNA Damage Response in BCR::ABL-Positive Leukemias

Amog Urs, PhD¹, Dimitrios Papaioannou, MD², Rohan Kulkarni, PhD³^*, Chinmayee Goda, PhD⁴^*, Remi Buisson⁵^*, Deedra Nicolet, MS⁶^*, Lauren Woodward⁷^*, Krzysztof Mrózek, MD, PhD⁶, Gregory K Behbehani, MD, PhD⁸, Sakari Kauppinen⁹^*, Ann-Kathrin Eisfeld, MD⁶, Iannis Aifantis, PhD¹⁰, Guramrit Singh¹¹^*, Adrienne M. Dorrance, PhD¹² and Ramiro Garzon, MD¹³^*

¹Huntsman Cancer Institute At the University of Utah, Salt Lake City, UT
²Perlmutter Cancer Center, Department of Medicine, Division of Hematology/Oncology, NYU Grossman School of Medicine, New York, NY, New York, NY
³Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT
⁴Huntsman Cancer Institute, Salt Lake City
⁵Department of Biological Chemistry, University of California Irvine, Irvine, CA
⁶The Ohio State University Comprehensive Cancer Center, Columbus, OH
⁷New York University School of Medicine, New York
⁸Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
⁹Aalborg University, Copenhagen, DNK
¹⁰Department of Pathology, NYU Grossman School of Medicine, New York, NY
¹¹The Ohio State University, Columbus
¹²Huntsman Cancer Institute at the University of Utah, Salt Lake City
¹³Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah Health, Salt Lake City, UT

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^*signifies non-member of ASH

602.O2.3 602. Myeloid Oncogenesis: Basic: CRISPR Screens and Other New Approaches to Understanding Myeloid Neoplasia