64th ASH Annual Meeting and Exposition: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Targeted Protein Degradation and Emerging Small Molecule Inhibitors in Myeloid Neoplasms

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

Research, Acute Myeloid Malignancies, AML, Fundamental Science, Translational Research, Non-Biological therapies, assays, CML, bioinformatics, Chemotherapy, Combination therapy, drug development, Chronic Myeloid Malignancies, Diseases, Therapies, metabolism, computational biology, Biological Processes, Myeloid Malignancies, Technology and Procedures, gene editing, molecular biology, profiling, omics technologies

343-345 (Ernest N. Morial Convention Center)

Moderators:

Elvin Wagenblast, Icahn School of Medicine and Valeria Visconte, PhD, Cleveland Clinic

Disclosures:

No relevant conflicts of interest to declare.

This Session was Assembled to Reflect the Content of the Selected Abstract. The Topics Span from Novel Therapeutic Strategies Based on the Design of Pharmacologic Degraders to Proteolysis-Targeted Chimera (PROTAC) Approaches. The Latter are Emerging Tools for Drug Targeting. In Addition, Novel Small Molecule Inhibitors Serving as Splicing Modulators or Acting Against Nucleic Binding Protein will be Presented. In Vivo Studies are Also Presented in the Abstracts # 4, 5, and 6.

2:00 PM

199

C-MYC Targeting By Degradation: Novel Dual c-Myc/GSPT1 Degrader GT19715 Induces TP53-Independent Cell Death in Acute Myeloid Leukemia and Lymphomas

Yuki Nishida, MD, PhD¹, Darah A Scruggs, MS¹^*, Edward Ayoub, PhD¹^*, Tallie Patsilevas, BS²^*, Vivian Ruvolo, MS²^*, Po Yee Mak¹^*, Bing Z Carter, PhD¹, Steffen Boettcher³^*, Abhishek Maiti, MBBS², Qianxiang Zhou, PhD⁴^*, Zhaohui Yang, PhD⁴^*, Honghua Yan, PhD⁴^*, Liandong Ma, MD⁴ and Michael Andreeff, MD, PhD¹

¹Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
³Department of Medical Oncology and Hematology, University of Zurich and University Hospital of Zurich, Zurich, Switzerland
⁴Kintor Pharmaceutical Limited, Suzhou, China

2:15 PM

200

LPA81: Discovery of an Exceptionally Potent Protac Degrading Native and Mutant BCR-ABL1 Oncoprotein in CML

Milad Rouhimoghadam, PhD¹^*, Hua Tang, PhD²^*, Junzhuo Liao, PhD²^*, Briana Bates, MSc¹^*, Daniela Uribe-Cano, BS¹^*, Helong Zhao, PhD^1,3^*, Weiping Tang, PhD^2,4^* and Michael W. Deininger, MD, PhD^1,3

¹Versiti Blood Research Institute, Milwaukee, WI
²School of Pharmacy, University of Wisconsin-Madison, Madison, WI
³Medical College of Wisconsin, Milwaukee, WI
⁴Department of Chemistry, University of Wisconsin-Madison, Madison, WI

2:30 PM

201

Imetelstat-Mediated Alterations in Lipid Metabolism to Induce Ferroptosis As Therapeutic Strategy for Acute Myeloid Leukemia

Claudia Bruedigam, PhD^1,2, Amy H Porter²^*, Axia Song²^*, Gerjanne Vroeg in de Wei²^*, Thomas Stoll, PhD²^*, Jasmin Straube, PhD^1,2^*, Leanne T Cooper²^*, Guidan Cheng²^*, Vivian FS Kahl, PhD^3,4^*, Alexander Sobinoff, PhD³^*, Victoria Y Ling, MD, PhD^1,2^*, Billy Michael Chelliah Jebaraj, PhD⁵^*, Laura J Bray, PhD⁶^*, Lars Bullinger, MD⁷, Florian H Heidel, MD⁸, Glen A Kennedy, MBBS, FRACP, FRCPA⁹^*, Michelle M Hill, PhD²^*, Hilda Pickett, PhD³^*, Omar Abdel-Wahab, MD¹⁰, Gunter Hartel, PhD¹¹^* and Steven W Lane, MD, PhD^1,2,12

¹School of Biomedical Sciences, The University of Queensland, Brisbane, Australia
²Cancer Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia
³Telomere Length Regulation Unit, Children’s Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, Australia
⁴Cancer Cell Biology, The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Woolloongabba, Australia
⁵Department of Internal Medicine III, University of Ulm, Ulm, Baden Wurttemberg, Germany
⁶Faculty of Engineering, School of Mech., Medical & Process Engineering, Queensland University of Technology, Brisbane, Australia
⁷Charité Universitätsmedizin Berlin, Hematology, Oncology and Tumor Immunology, Berlin, Germany
⁸Hematology, Oncology, Stem Cell Transplantation and Palliative Care, University Medicine Greifswald, Greifswald, Germany
⁹Department of Haematology and BMT, Royal Brisbane and Women's Hospital, Brisbane, Australia
¹⁰Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
¹¹Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia
¹²Cancer Care Services, Royal Brisbane and Women's Hospital, Brisbane, Australia

2:45 PM

202

CTX-712, a Novel Splicing Modulator Targeting Myeloid Neoplasms

Akinori Yoda, PhD¹^*, Daisuke Morishita, PhD²^*, Yotaro Ochi, MD, PhD³^*, Akio Mizutani, PhD²^*, Takuto Mori, MD³^*, June Takeda, MD³^*, Hirokazu Tozaki, PhD²^*, Yoshihiko Satoh, PhD⁴^*, Yasuhito Nannya, M.D., Ph.D.³, Hideki Makishima, MD, PhD³, Hiroshi Miyake, PhD⁴^* and Seishi Ogawa, MD, PhD³

¹Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto City, Japan
²Chordia Therapeutics Inc., Fujisawa, Kanagawa, Japan
³Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
⁴Chordia Therapeutics Inc., Fujisawa, Japan

3:00 PM

203

Pre-Clinical Investigation of a Novel Small Molecule Inhibitor Targeting YBX1 in AML

Tina M Schnoeder, PhD¹^*, Florian Perner, MD¹, Ashok Kumar Jayavelu, PhD²^*, Lianghao Mao²^*, Qirui Zhang, PhD¹^*, Chen-Jen Hsu, MSc¹^*, Theresa Eifert, MSc¹^*, Uwe Grunwald, MD¹^*, Peter Mertens³^*, Dhanir Tailor^4,5^*, Akram Taherinasab⁶^*, Theodore P. Braun, MD, PhD^6,7, Sanjay Malhotra, PhD^4,5^* and Florian H. Heidel, MD^1,8

¹Klinik und Poliklinik für Innere Medizin C, Universitätsklinikum Greifswald, Greifswald, Germany
²Hopp Children’s Cancer Center, University Hospital Heidelberg, Heidelberg, Germany
³Otto-von-Guericke University Medical Center, Magdeburg, Germany
⁴Department of Cell, Development and Cancer Biology, Oregon Health & Science University, Portland, OR
⁵Center for Experimental Therapeutics, Knights Cancer Center Institute, Oregon Health and Science University, Portland, OR
⁶Division of Oncological Sciences, Oregon Health & Science University, Portland, OR
⁷Knight Cancer Institute, Oregon Health & Science University, Portland, OR
⁸Fritz-Lipmann Institute, Leibniz Institute on Aging, Jena, Germany

3:15 PM

204

Preclinical Efficacy of Novel Drug Combination Against AML with 3q26 Lesions and EVI1 Overexpression

Christine E Birdwell, PhD¹^*, Warren C. Fiskus, BSc, PhD², Tapan M. Kadia, MD³, Christopher Peter Mill, PhD, BA⁴, John A. Davis¹^*, Kaberi Das⁵^*, Naval Daver, MD⁴, Courtney D. DiNardo, MD, MSCE⁶, Koichi Takahashi, MD, PhD⁷, Koji Sasaki, MD⁶, Stephen Horrigan, PhD⁸^* and Kapil N. Bhalla, MD⁶

¹The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX
³Department of Leukemia, MD Anderson Cancer Center, Houston, TX
⁴MD Anderson Cancer Center, Houston, TX
⁵UT MD Anderson Cancer Center, Houston, TX
⁶Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁷Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX
⁸Iterion Therapeutics, Houston, TX

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^*signifies non-member of ASH

604.O3.6 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Targeted Protein Degradation and Emerging Small Molecule Inhibitors in Myeloid Neoplasms