66th ASH Annual Meeting: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Novel Approaches to Targeting Epigenetics, Apoptosis and Immune Effectors in Myeloid Malignancies

Symposia: Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms Oral and Poster Abstracts
Oral

Research, Acute Myeloid Malignancies, AML, Combination therapy, Antibody Therapy, Apoptosis, Adult, Translational Research, Drug development, Bispecific Antibody Therapy, Elderly, Chemotherapy, Genomics, Bioinformatics, Hematopoiesis, Pediatric, Diseases, Immune mechanism, Treatment Considerations, Biological therapies, Immunology, Non-Biological therapies, Metabolism, Myeloid Malignancies, Pharmacology, Biological Processes, Technology and Procedures, Molecular biology, Profiling, Study Population, Human, Animal model, Omics technologies

Grand Hall B (Manchester Grand Hyatt San Diego)

Moderators:

Jennifer N. Saultz, DO, Oregon Health & Science University and Nicole R. Grieselhuber, MD, PhD, The Ohio State University Wexner Medical Center

Disclosures:

No relevant conflicts of interest to declare.

2:00 PM

205

Posttranslational Changes in Histone Modification Driven By USP48 Loss Increase Sensitivity to Hypomethylating Agents in Acute Myeloid Leukemia

Constanze Schneider, PhD^1,2^*, Gabriela Alexe, PhD^1,2^*, Ashleigh Meyer¹^*, Lucy A Merickel¹^*, Allen T Basanthakumar¹^*, Audrey Taillon¹^*, Silvi Salhotra¹^*, Yara Rodriguez^1,2^*, Björn Häupl, PhD^3,4,5^*, David E. Root, PhD⁶^*, Thomas Oellerich, MD^5,7,8^* and Kimberly Stegmaier, MD^1,6,9

¹Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
²The Broad Institute of MIT and Harvard, Cambridge, MA
³Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
⁴German Cancer Research Center (DKFZ), Heidelberg, Germany
⁵Frankfurt Cancer Institute, Goethe University, Frankfurt, Germany
⁶Broad Institute of MIT and Harvard, Cambridge, MA
⁷German Cancer Consortium (DKTK), Partner site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Heidelberg, Germany
⁸Department of Medicine 2 - Hematology and Oncology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
⁹Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA

2:15 PM

206

Synergistic Efficacy of Dual Menin and PRMT5 Targeting Against NPM1 mutatedand KMT2A-rearranged Leukemia

Nadezda Dolgikh, PhD^1,2^*, Johanna Rausch, MD^2,3^*, Marlene Steiner, PhD³^*, Jonas Schönfeld³^*, Catharina Lahrmann³^*, Nina Hilke³^*, Maria Alejandra Vila Molerio³^*, Simon Weisemann, MD³^*, Maria Saura-Pañella, M.Sc.⁴^*, Aarón Gallego-Crespo, M.Sc.³^*, Matthias Theobald, MD⁵, Daniel Sasca, MD⁵^*, Chun-Wei David Chen, PhD^6,7 and Michael W.M. Kühn, MD³^*

¹Department of Medicine III, University Medical Center, Johannes Gutenberg-University, Mainz, AL, Germany
²German Cancer Consortium (DKTK) Frankfurt/Mainz, Mainz, Germany
³Department of Medicine III, University Medical Center, Johannes Gutenberg-University, Mainz, Germany
⁴Department of Hematology and Oncology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
⁵Department of Hematology and Oncology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
⁶Department of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA
⁷Department of Systems Biology, Beckman Research Institute, Duarte, CA

2:30 PM

207

Enhancing Macrophage Mediated Phagocytosis in AML: The Complementary Mechanisms of Venetoclax and Azacitidine Combination Therapy

Zhe WANG, MD¹^*, Xufeng Chen, PhD², Simone Sidoli, PhD³^*, Anna Skwarska, PhD⁴, Yannan Jia^1,5^*, Lei Yang⁶^*, Varun Gupta, Masters in Bioinformatics⁴^*, Shikhar Sharma⁴^*, Iannis Aifantis, PhD², Hussein A. Abbas, MD, PhD¹, Naval Daver, MD¹, Qi Zhang Tatarata, MD, PhD^1,7^* and Marina Konopleva^4,8

¹Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Pathology, NYU Grossman School of Medicine, New York, NY
³Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY
⁴Department of Oncology, Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY
⁵Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
⁶UTHealth Houston Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX
⁷NYC Health + Hospital/ Kings County Hospital, SUNY Downstate Health Sciences University, Brooklyn, NY
⁸MD Anderson - former employer, Houston, TX

2:45 PM

208

CBX250 Is a Novel Cathepsin G Peptide-HLA-Targeting T Cell Engager That Exhibits High Tumor Antigen Selectivity and Potent Antileukemic Activity In Vivo

Benjamin H. Lee, MD, PhD¹, Geraldine Paulus, PhD¹^*, Jennifer Helble, PhD¹^*, Preethi Sankaran, MS¹^*, Tanzila Rahman, MS¹^*, Delainey O'Connor, MS¹^*, Melissa Bikowitz, PhD¹^*, Sarah Jaffe, BS¹^*, Alona Kulesha, PhD¹^*, Bhupal Ban, PhD¹^*, Nga Sze Amanda Mak, PhD¹^*, Michael Princiotta, PhD¹^*, Chunhua Shi, PhD²^*, Jun Yan, PhD²^*, Hong He, MD, PhD³^*, Ningping Feng, PhD⁴^*, Jeffrey J. Molldrem, MD⁵, Timothy Heffernan, PhD⁶^*, Gheath Alatrash, PhD, DO⁷ and Dmitri Wiederschain, PhD¹^*

¹Crossbow Therapeutics, Cambridge, MA
²Oncology Research for Biologics and Immunotherapy Translation (ORBIT), University of Texas MD Anderson Cancer Center, Houston
³Department of Hematopoietic Biology and Malignancy, University of Texas M.D. Anderson Cancer Center, Houston, TX
⁴University of Texas MD Anderson Cancer Center, Houston, TX
⁵Departments of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
⁶The University of Texas MD Anderson Cancer Center, Houston, TX
⁷Department of Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Pearland, TX

3:00 PM

209

Identification of DLK1 As a Novel Therapeutic Target in Down Syndrome Myeloid Leukemia

Sonali P Barwe, PhD, MSc¹, Meredith Tavenner²^*, Patrick Van Berkel, PhD³^*, Aimy Sebastian⁴^*, Rhonda E. Ries, MA⁵^*, Soheil Meshinchi, MD, PhD⁵, Johann K. Hitzler, MD⁶, Yana Pikman, MD⁷, Anders Kolb, MD² and Anilkumar Gopalakrishnapillai, PhD, MSc²

¹Nemours Children's Hospital, Wilmington, DE
²Lisa Dean Moseley Foundation Institute for Cancer and Blood Disorders, Nemours Children's Hospital, Wilmington, DE
³ADC Therapeutics Ltd, London, United Kingdom
⁴Lawrence Livermore National Laboratory, Livermore, CA
⁵Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA
⁶The Hospital for Sick Children, Toronto, ON, Canada
⁷Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA

3:15 PM

210

Disrupting Mitochondrial Dynamics and Metabolism in Leukemic Stem Cells through Mitochondrial PCNA Inhibition: The Role of AOH1996

Hyunjun Kang, PhD¹^*, Melissa Valerio²^*, Jia Feng³^*, Long Gu, PhD⁴^*, Dinh Hoa Hoang²^*, Shawn Sharkas⁵^*, Khyatiben V. Pathak⁶^*, Jennifer Jossart, PhD⁴^*, Yuriy Shostak, PhD⁷^*, Zhuo Li, PhD⁸^*, Bin Zhang⁵, Patrick Pirrotte⁶^*, Jefferson Perry, PhD⁴^*, Robert Hickey, PhD⁹^*, Linda H Malkas, PhD⁴^*, Guido Marcucci¹⁰ and Le Xuan Truong Nguyen^6,11^*

¹Department of Hematologic Malignancies Translational Science, City of Hope National Medical Center, Duarte, CA
²Department of Hematologic Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA
³Department of Hematologic Malignancies Translational Science, Beckman Research Institute and City of Hope National Medical Center, Duarte, California, USA, Duarte
⁴Department of Molecular Diagnostics & Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA, Duarte
⁵Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA
⁶Cancer & Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ
⁷City of Hope Medical Center, Monrovia, CA
⁸Beckman Research Institute, City of Hope National Medical Center, Duarte, California, USA, Duarte
⁹Department of Cancer Biology & Molecular Medicine, Beckman Research Institute of City of Hope, Duarte, CA, USA, Duarte
¹⁰Department of Hematologic Malignancies Translational Science, Duarte, CA
¹¹Department of Hematologic Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope National Medical Center and Beckman Research Institute, South El Monte, CA

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^*signifies non-member of ASH

604A.O2.6 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Novel Approaches to Targeting Epigenetics, Apoptosis and Immune Effectors in Myeloid Malignancies