66th ASH Annual Meeting: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II

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

Research, Antibody Therapy, Acute Myeloid Malignancies, Combination therapy, AML, Fundamental Science, Apoptosis, Adult, Bispecific Antibody Therapy, Drug development, APL, MPN, Translational Research, Elderly, Genomics, Bioinformatics, Drug-drug interactions, Hematopoiesis, Chronic Myeloid Malignancies, CMML, Diseases, Immune mechanism, Treatment Considerations, Biological therapies, Immunology, Immunotherapy, Adverse Events, Metabolism, Computational biology, Biological Processes, Myeloid Malignancies, Emerging technologies, Monoclonal Antibody Therapy, Technology and Procedures, Gene editing, Molecular biology, Study Population, Multi-systemic interactions, Human, Pathogenesis, Animal model

Halls G-H (San Diego Convention Center)

2749

Efficacy of a Novel BCL-XL Degrader, DT2216, in Preclinical Models of Post-Myeloproliferative Neoplasm Secondary AML

Zhe Wang, MD, PhD¹^*, Anna Skwarska, PhD², Gowri Poigailwar²^*, Sovira Chaudhry, MSc²^*, Alba Rodriguez-Meira, PhD^3,4^*, Pinpin Sui, PhD⁵^*, Emmanuel Olivier, PhD^6,7^*, Yannan Jia^1,8^*, Cassandra L. Ramage¹^*, Guangrong Zheng, PhD⁹^*, Alexandra Schurer, MS², Kira Gritsman, MD, PhD¹⁰, Eirini Papapetrou, MD, PhD^6,7, Kapil N. Bhalla, MD¹, Daohong Zhou, MD¹¹^*, Adam J Mead, MBBChir¹², Raajit Rampal, MD, PhD¹³, Jeffrey W Tyner, PhD¹⁴^*, Hussein A. Abbas, MD, PhD¹, Naveen Pemmaraju, MD¹⁵, Qi Zhang Tatarata, MD, PhD^1,16^* and Marina Konopleva, MD^1,2

¹Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Oncology, Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY
³Broad Institute of MIT and Harvard, Cambridge, MA
⁴Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA
⁵Department of Cell Systems & Anatomy, The University of Texas Health Science Center at San Antonio, San Antonio, TX
⁶Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY
⁷Center for the Advancement of Blood Cancer Therapies, Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
⁸Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
⁹Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL
¹⁰Albert Einstein College of Medicine, Bronx, NY
¹¹Department of Biochemistry and Structural Biology and Center for Innovative Drug Discovery, University of Texas Health Science Center at San Antonio, San Antonio, TX
¹²Medical Research Council (MRC) Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, National Institute for Health Research Biomedical Research Centre, University of Oxford, Oxford, United Kingdom
¹³Memorial Sloan Kettering Cancer Center, New York, NY
¹⁴Knight Cancer Institute, Oregon Health & Science University, Portland, OR
¹⁵Department of Leukemia, The University of Texas MD Anderson Cancer Center, Bellaire, TX
¹⁶NYC Health + Hospital/ Kings County Hospital, SUNY Downstate Health Sciences University, Brooklyn, NY

2750

Preclinical Characterization of the Anti-Leukemia Activity of the CD123 Antibody-Drug Conjugate, Pivekimab Sunirine (IMGN632)

Frances M. Cole¹^*, George S. Laszlo, PhD²^*, Margaret C. Lunn-Halbert¹^*, Allie R. Kehret¹^*, Patrick A. Zweidler-McKay, MD, PhD³, Eduardo Rodríguez-Arbolí, MD, MPhil^1,4^*, David Wu, MD, PhD⁵^*, Kyle E. Nyberg¹^*, Junyang Li¹^*, Sheryl Y. T. Lim, DPhil¹^*, Sribalaji Lakshmikanthan, PhD³^* and Roland B. Walter, MD, PhD, MS^6,7,8

¹Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA
²1100 Fairview Avenue North, Fred Hutchinson Cancer Center, Seattle, WA
³ImmunoGen, Inc., Waltham, MA
⁴Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, University of Seville, Seville, Spain
⁵Hematopathology, University of Washington, Seattle, WA
⁶Fred Hutchinson Cancer Center, Seattle, WA
⁷Department of Medicine, Division of Hematology and Oncology, University of Washington, Seattle, WA
⁸Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA

2752

Molecular Mechanisms Associated with Autophagy Inhibition to Overcome Resistance to FLT3 Inhibitors

Manuela Albuquerque De Melo, MSc¹^*, Diego A. Pereira-Martins, Ph.D.²^*, Brunno Gilberto Santos Macedo, MSc¹^*, Livia Bassani Lins de Miranda, Bsc³^*, Priscila Santos Scheucher, PhD¹^*, Isabel Weinhäuser, PhD⁴^*, Gerwin Huls², Jan Jacob Schuringa, Prof. Dr.², João Agostinho Machado-Neto, PhD³^* and Fabiola Traina, MD, PhD¹

¹Department of Medical Images, Hematology, and Oncology, University of São Paulo at Ribeirão Peto Medical School, Ribeirão Preto, Brazil
²Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, Groningen, Netherlands
³Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
⁴Department of Experimental Hematology, University Medical Center Groningen, Groningen, Netherlands

2753

Elucidating Transcriptional Heterogeneity in Venetoclax Resistant AMLs

Vakul Mohanty, PhD¹^*, Natalia Baran, MD, PhD^2,3, Yuefan Huang⁴^*, Cassandra L. Ramage²^*, Laurie Cooper⁵^*, Sarah Gwen Pelletier, BS²^*, Shan He⁴^*, Ramiz Iqbal⁴^*, May Daher, MD, MD⁶, Jeffrey W. Tyner, PhD⁷, Gordon B Mills⁸^*, Marina Konopleva, MD⁹ and Ken Chen, PhD¹^*

¹Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
³Section of Experimental Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
⁴Department of Bioinformatics and Computational biology, The University of Texas MD Anderson Cancer Center, Houston, TX
⁵The University of Texas MD Anderson Cancer Center, Houston
⁶Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
⁷Knight Cancer Institute, Oregon Health & Science University, Portland, OR
⁸Division of Oncological Sciences, Knight Cancer Institute, Oregon Health & Science University, Portland, OR
⁹Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY

2754

Vincristine Overcomes Cytarabine Resistance in Acute Myeloid Leukemia By Suppression of ARHGAP18-Mediated Cellular Senescence

Xiyang Ren¹^*, Haotian Yan¹^*, Mei Zhou¹^*, Fan Wu²^*, Qing Zhang¹^*, Yangyang Ding, MD³^*, Qian Li, MD⁴^*, Huiping Wang⁵^*, Caixian Xu⁵^*, Jiyu Wang⁶^*, Cong Li²^*, Wanqiu Zhang²^*, Linlin Liu¹^*, Ruotong Chen⁵^*, Yi Dong¹^*, Wenjie Dai⁵^*, Zhimin Zhai, MD⁷ and Qianshan Tao, MD⁸^*

¹The Second Affiliated Hospital of Anhui Medical University, Hefei, China
²Hematologic Department/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
³Hematologic Department/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
⁴Center of Hematology Research, Anhui Medical University, Hefei, China
⁵Department of Hematology, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
⁶Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, AL, China
⁷The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
⁸Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China

2755

Targeting Co-Regulatory Feedback Loop of MYC and GSPT1 By MYC/GSPT1 Dual Degradation Is Synthetic Lethal in Combination with Ven/Aza in TP53 Mutant Acute Myeloid Leukemia Stem and Progenitor Cells

Yuki Nishida, MD, PhD¹, Hideaki Mizuno, MD, PhD¹^*, Edward Ayoub, PhD¹^*, Eiji Sugihara, PhD²^*, Lauren B. Ostermann, BSc¹^*, Shayaun Khazaei, BS¹^*, Darah Scruggs, MS¹^*, Po Yee Mak¹^*, Baozhen Ke, BS¹^*, Bing Z. Carter, PhD¹, Abhishek Maiti, MBBS³, Liandong Ma, PhD⁴^* and Michael Andreeff, MD, PhD¹

¹Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Fujita Health University, Division of Gene Regulation, Cancer Center and Open Facility Center, Research Promotion Headquarters, Toyoake, JPN
³Department of Leukemia, The University of Texas Health Science Center At Houston, Houston, TX
⁴Oncobiotherapeutics, Radnor, PA

2756

PTPN12 Is Targetable and Context-Specific TSG in -7/del7q Myeloid Neoplasia

Daniel J Vail¹^*, Jill Durkin²^*, Dongxu Jiang, PhD¹, Thomas Laframboise, PhD³^* and Babal K. Jha, PhD^1,4

¹Center for Immunotherapy & Precision Immuno-Oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH
²Center for Immunotherapy & Precision Immuno-Oncology, Lerner Research Institute, Cleveland Clinic, Bay Village, OH
³Case Western Reserve University, Cleveland, OH
⁴Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH

2757

Integrative Analysis of Transcriptomic and Proteomic Data Identifies Patterns of Primary Resistance to Venetoclax-Azacitidine and Reveals Targetable Vulnerabilities in Acute Myeloid Leukemia (AML)

Ida Vänttinen^1,2^*, Joseph Saad, MSc^1,2^*, Tanja Ruokoranta, MSc²^*, Sari Kytölä, MD³^*, Pia-Sofia Ettala, MD⁴^*, Marja Pyörälä, MD, PhD⁵^*, Johanna Rimpiläinen, MD⁶^*, Timo Siitonen, MD, PhD⁷^*, Caroline A. Heckman, PhD^1,2, Heikki Kuusanmäki, PhD^1,2,8^* and Mika Kontro, MD, PhD^1,2,3,8

¹iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland
²Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
³Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
⁴Department of Clinical Hematology, Turku University Hospital, Turku, Finland
⁵Department of Medicine, Kuopio University Hospital, Kuopio, Finland
⁶Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
⁷Department of Hematology, Oulu University Hospital, Oulu, Finland
⁸Foundation for the Finnish Cancer Institute, Helsinki, Finland

2758

Combined CXCR-4 Inhibition with Novel Agent GPC-100 (burixafor) and Beta 2 Adrenergic Receptor Blockade Enhances Cytarabine Response for Acute Myeloid Leukemia Blasts on Stroma

Yueming Tang, MD, PhD¹^*, Adam Braun, MD²^*, Zachary von Behren³^*, Jieya Wu, MD⁴^*, Caitlyn Haley³^*, Chunxiao Zhang, PhD⁵^*, Brenda Loera⁵^*, Pina M. Cardarelli, Ph.D.⁶, Nina Caculitan, PhD⁶^*, Sylvia Chien⁷^*, Jin Dai, PhD⁷^*, Vivian G. Oehler, MD⁸^*, Jianying Zhang, PhD⁹^*, Guido Marcucci¹⁰ and Pamela S. Becker, MD, PhD^11,12

¹Department of Hematologic Malignancies Translational Science, City of Hope, Monrovia, CA
²City of Hope, Duarte, CA
³City of Hope, Monrovia, CA
⁴Department of Hematologic Malignancies Translational Science, City of Hope National Medical Center, Monrovia, CA
⁵Amgen, Thousand Oaks, CA
⁶GPCR Therapeutics, Redwood City, CA
⁷University of Washington, Seattle, WA
⁸Translational Science and Therapeutics, Fred Hutchinson Cancer Center, Seattle, WA
⁹Department of Computational and Quantitative Medicine, Duarte, CA
¹⁰Department of Hematological Malignancies Translational Science, Gehr Family Center for Leukemia Research, City of Hope Medical Center and Beckman Research Institute, Duarte, CA
¹¹Department of Hematologic Malignancies Translational Science, City of Hope Beckman Research Institute, Duarte, CA
¹²Hematology/HCT, City of Hope, Duarte, CA

2759

ERK1/2 Inhibition Mediates Bax Dependent Proteolysis of OPA1 and Induces Mitochondrial Cristae Remodeling to Overcome Resistance to Venetoclax

Priyanka Sharma, PhD¹, Natalia Baran, MD, PhD², Qi Zhang, PhD²^*, M. Anna Zal, M.Sc.³^*, Joanne Munck, PhD⁴^*, Martin Sims, PhD⁴^*, Bing Z. Carter, PhD¹, Michael Andreeff, MD, PhD¹ and Gautam Borthakur, MD¹

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
³Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX
⁴Astex Pharmaceuticals, Cambridge, United Kingdom

2760

Anti-Leukemia Combinatorial Efficacy of ABBV155, a B7H3-BCL-XL Inhibitor Antibody-Drug Conjugate, in Combination with Venetoclax through BCL-XL/BIM and BCL-2/BIM Complex Dissociations

Zhe Wang, MD, PhD¹^*, Cassandra L. Ramage¹^*, Helen Ma¹^*, Haichao Zhang²^*, Andrew Souers, PhD³, Darren C Phillips, PhD, BSc²^*, Marina Konopleva, MD⁴ and Qi Zhang Tatarata, MD, PhD^1,5^*

¹Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Abbvie, North Chicago, IL
³AbbVie Inc., North Chicago, IL
⁴Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY
⁵NYC Health + Hospital/ Kings County Hospital, SUNY Downstate Health Sciences University, Brooklyn, NY

2761

M2-like Macrophages Transfer Mitochondria to Acute Myeloid Leukaemia Cells Via Tunnelling Nanotubes Promoting Therapy Resistance

Ebubechukwu Osinachi Nwarunma, MSc, BSc¹^*, Katerina Miari, PhD²^*, Athanasia Papadopoulou, MSc³^*, Leandro Martinez, PhD⁴^*, Victoria Campbell, MD, PhD⁵^*, Samantha Hurwitz, PhD⁶, Tatiana Fourfouris, MSc⁶, Ki Jun Lee, MSc⁶, Carl Goodyear, PhD⁷^*, Theodoros Simakou, PhD⁷^*, Marcus Doohan, BSc⁷^*, Lucy MacDonald, PhD⁷^*, Timothy Humpton, PhD^3,8^*, Lesley Forrester, PhD⁹^*, Mariola Kurowska-Stolarska, PhD⁷^*, Ken I Mills, PhD, FRCPath¹⁰, Yong-Mi Kim, MD, PhD, MPH⁶, Helen Wheadon, PhD²^*, Monica L Guzman, PhD¹¹ and Mark T Williams, PhD^3,12^*

¹Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, SCO, United Kingdom
²Paul O’Gorman Leukaemia Research Centre, School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom
³Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, United Kingdom
⁴Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY
⁵Department of Haematology, Western General Hospital, Edinburgh, United Kingdom
⁶Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA
⁷School of Infection & Immunity, University of Glasgow, Glasgow, United Kingdom
⁸Cancer Research UK Scotland Institute, Glasgow, United Kingdom
⁹Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, United Kingdom
¹⁰Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, NI, United Kingdom
¹¹Weill Cornell Medicine and The New York Presbyterian Hospital in New York City, New York, NY
¹²School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom

2762

Inhibition of Peroxisome Proliferation-Activated Receptor Delta (PPARδ) Selectively Kills Acute Myeloid Leukemia Cells

Yingying Yang, MSc¹^*, Ekaterina Parfenova², Nikolina Vrdoljak, BSc³^*, Mark D. Minden, MD, PhD^4,5,6,7,8^*, Jessica Luc⁹^*, Andrew Doxey, Ph.D.⁹^* and Paul A. Spagnuolo, PhD¹⁰^*

¹Food Science, University of Guelph, Guelph, ON, Canada
²Department of Food Science, University of Guelph, Guelph, ON, CAN
³Department of Food Science, University of Guelph, Georgetown, ON, Canada
⁴Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
⁵Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
⁶Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
⁷Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
⁸Princess Margaret Cancer Centre / University Health Network, Toronto, ON, Canada
⁹Department of Biology, University of Waterloo, Waterloo, ON, Canada
¹⁰Department of Food Science, University of Guelph, Guelph, ON, Canada

2763

HPK1 Inhibition and Venetoclax Combination Suppressed AML By Enhancing Cytotoxic T-Cell Response to Leukaemia

Xiaoyuan Zeng^1,2^*, Kwui-Wa Tong^1,2^*, Koon Chuen Chan^1,2^*, Li-Chuan Zheng^1,2^*, Stephen Lam, PhD, MBBS,¹^*, Mark Robert Bray, PhD³^*, Tak-Wah Mak, PhD^2,3,4^*, Cheuk-Him Man, PhD¹^* and Anskar Y. H. Leung, MD, PhD^1,2

¹Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
²Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong, China
³Princess Margaret Cancer Centre, The Campbell Family Institute for Breast Cancer Research, Toronto, Canada
⁴Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

2764

The Transcription Factor IRF8 Regulates the Sensitivity of AML Cells to LSD1 Inhibition and All-Trans Retinoic Acid

Emily E Hartung^1,2^*, Kanwaldeep Singh, PhD^1,3^*, Sarah Coopersmith, BSc^1,2^*, Jamie Avrumutsoae^1,2^*, Siddaarth Varatharajan^1,2^*, Sara Pishyar, MSc^1,2^*, Pradhariny Prabagaran, MSc^1,2^*, Dina Khalaf, MSc, MBBS³, Alejandro Garcia-Horton, MD³, Ronan Foley, MD, FRCPC³^*, Brian Leber, MD⁴, Irwin Walker, MBBS⁴, Kylie L. Lepic, MD³^*, Maria Kleppe, PhD, RPh⁵^*, Hugh Young Rienhoff Jr., MD⁵ and Tobias Berg, MD^1,3,6

¹Centre for Discovery in Cancer Research, McMaster University, Hamilton, ON, Canada
²Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
³Department of Oncology, McMaster University, Hamilton, ON, Canada
⁴Department of Medicine, McMaster University, Hamilton, ON, Canada
⁵Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., Rahway, NJ
⁶Escarpment Cancer Research Institute, Hamilton Health Sciences / McMaster University, Hamilton, ON, Canada

2765

Molecular Interactions between Mitochondrial Ferroptosis and Apoptosis Pathways in Acute Myeloid Leukemia

Kazuharu Kamachi¹^*, Hiroki Akiyama, MD, PhD^1,2, Ran Zhao, MSc¹^*, Liang Zhang, PhD¹^*, Saurabh Kumar Gupta, PhD¹^*, Lauren B. Ostermann, BSc¹^*, Yuji Otsuki, MD, PhD³^*, Osamu Nagano, DDS, PhD³^*, Hideyuki Saya, MD, PhD³^*, Ayumu Taguchi, MD, PhD⁴^*, Michael Andreeff, MD, PhD¹ and Jo Ishizawa, MD, PhD¹

¹Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan
³FerroptoCure, Tokyo, Japan
⁴Division of Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan

2766

Transcriptomic Signature of Resistance to Decitabine/Venetoclax in AML Patients

Abdullah Khasawneh¹^*, Faith Jessica Paran, PhD²^*, Abhishek Maiti, MBBS³, Bofei Wang, PhD⁴, Kala Hayes, PhD⁵^*, Courtney D. DiNardo, MD, MSc⁶, Michael Andreeff, MD, PhD⁷, Hussein A. Abbas, MD, PhD⁵, Marina Konopleva, MD^5,8 and Yoko Tabe, MD, PhD^9,10^*

¹Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Bunkyo, Japan
²Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
³Department of Leukemia, The University of Texas Health Science Center At Houston, Houston, TX
⁴Department of Leukemia, Division of Cancer Medicine, The University of Texas At MD Anderson Cancer Cent, Houston, TX
⁵Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁶Department of Leukemia, UT MD Anderson Cancer Center, Houston, TX
⁷Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁸Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY
⁹Department of Clinical Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
¹⁰Department of Leukemia, The University of Texas MD Anderson Cancer Center, Tokyo, Japan

2767

The Proteostasis Network Is a Therapeutic Target in Acute Myeloid Leukemia

Kentson Lam, MD, PhD, BA¹, Yoon Joon Kim²^*, Carlo M. Ong²^*, Andrea Z. Liu²^*, Fanny Jiahua Jiahua Zhou, BS, MS³, Bernadette A. Chua, PhD²^*, Silvia Vicenzi, PhD⁴, Pierce W. Ford⁵^*, Jie-Hua Zhou⁶^*, Eric Bennett⁵^*, Leslie A Crews, PhD⁷, Edward D. Ball, MD⁶ and Robert Signer, PhD⁸

¹Division of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, San Diego, CA
²Division of Regenerative Medicine, Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California, San Diego, La Jolla, CA
³Division of Regenerative Medicine, Department of Medicine, Stem Cell Discovery Center, Sanford Stem Cell Institute, Moores Cancer Center, University of California San Diego, San Diego, CA
⁴Moores Cancer Center, UNIVERSITY CALIFORNIA, SAN DIEGO, La Jolla, CA
⁵Department of Cell and Developmental Biology, University of California at San Diego, School of Biological Sciences, La Jolla, CA
⁶Division of Bone and Marrow Transplantation, Department of Medicine, Moores Cancer Center, University of California, San Diego, La Jolla, CA
⁷Division of Regenerative Medicine, UCSD, La Jolla, CA
⁸University of California San Diego, La Jolla, CA

2768

Combined Use of Ziftomenib and Selinexor Is Effective in NPM1 Mutant Acute Myeloid Leukemia

Sandhya Dhiman¹, Md. Hafiz Uddin²^*, Vikram Dhillon, DO, MBA^3,4,5^*, Jeff Justin Aguilar, MD, MBA⁶, Amro Aboukameel²^*, Husain Khan²^*, Sahar Bannoura⁷^*, Jay Yang, MD⁸, Gregory Dyson, PhD⁹^*, Steven Buck¹⁰^*, Asfar Azmi²^*, Lisa Polin, PhD^11,12^*, Francis Burrows, PhD¹³^*, Linda Kessler, BA¹³^*, Jaroslaw Maciejewski¹⁴ and Suresh Kumar Balasubramanian, MD¹⁵

¹Karmanos Cancer Institute/Wayne State University, Detroit, MI
²Karmanos Cancer Institute/ Department of Oncology, Wayne State University, Detroit, MI
³Department of Hematology/Oncology, Neal Cancer Center/Houston Methodist Hospital, Detroit, MI
⁴Department of Hematology/Oncology, Neal Cancer Center/Houston Methodist Hospital, Houston, TX
⁵Department of Oncology, Karmanos Cancer Center/Wayne State University, Detroit, MI
⁶Department of Internal Medicine, Detroit Medical Center, Detroit, MI
⁷Karmanos Cancer Institute/ Department of Oncology, Detroit, MI
⁸Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI
⁹Karmanos Cancer Institute/Department of Oncology, Wayne State University, Detroit, MI
¹⁰Wayne State University, Detroit, MI
¹¹Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
¹²Department of Oncology, Wayne State University School of Medicine, Detroit, MI
¹³Kura Oncology, Carlsbad
¹⁴Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
¹⁵Department of Oncology, Karmanos Cancer Institute/ Wayne State University, Detroit, MI

2769

Unraveling How Treatment Shapes Clonal Evolution and Resistance in Murine KMT2A-Rearranged Leukemia with Subclonal Kras^G12D

Ton Falques, PhD^*, Mattias Pilheden, PhD^*, Larissa Helena Moura-Castro, PhD^*, Qirui Zhang, PhD^*, Louise Ahlgren, PhD^*, Helena Sturesson, PhD^*, Kajsa Paulsson, PhD, Axel Hyrenius Wittsten, PhD^* and Anna K. Hagstroem-Andersson, PhD

Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund, Sweden

2770

Preclinical Activity of RAS(ON) Multi-Selective Inhibitor RMC-7977 and Therapeutic Combinations in AML with Signaling Mutations

Bogdan Popescu, MD¹^*, Madison Piao²^*, Sydney Abelson³^*, Carolina E. Morales, BS³^*, Khadija Yousuf³^*, Jose M. Rivera³^*, Cheryl A C Peretz, MD³, Elliot Stieglitz, MD, PhD³ and Catherine C. Smith, MD²

¹Department of Medicine, Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA
²Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA
³Division of Hematology-Oncology, Dept. of Pediatrics, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA

2771

Preclinical Evaluation of Stx-0712, a CCR2 Cytotoxicity Targeting Chimera (CCR2-CyTAC) for the Treatment of Chronic Myelomonocytic Leukemia

Brandon Turunen, PhD¹^*, Craig Leach, PhD¹^*, Matthew Smith²^*, Terra L. Lasho, PhD², Christy Finke, BS³^*, Abhishek A. Mangaonkar, MBBS², Aref Al-Kali, MD², Yael Kusne, MD, PhD⁴, Talha Badar, MD⁵, James M. Foran, MD⁶, Aisha Margaert⁷^*, Michelle Baptista¹^*, Stephanie Wiltzius¹^* and Mrinal M. Patnaik, MD, MBBS²

¹Solu Therapeutics, Boston
²Mayo Clinic, Rochester, MN
³Division of Hematology, Mayo Clinic, Rochester, MN
⁴Mayo Clinic, Phoenix, AZ
⁵Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL
⁶Division of Hematology & Medical Oncology, Mayo Clinic, Jacksonville, FL
⁷Discovery Life Sciences, Seattle

2772

First-in-Class Targeted Protein Degrader of MLLT1/3 for the Treatment of Advanced AML and ALL Including Menin Inhibitor Resistant / Refractory Disease

John Pollard¹^*, Graham Craggs¹^*, Gillian Farnie²^*, Matthew Fawkes¹^*, Fenella Gross¹^*, Joe Harman¹^*, Marta Llorca-Cardenosa¹^*, Sarah Major¹^*, Alison Maloney, PhD³^*, Thomas A Milne⁴ and Iain Simpson¹^*

¹Dark Blue Therapeutics, OXFORD, United Kingdom
²Cancer Research Horizons, The Francis Crick Institute, London, United Kingdom
³Dark Blue Therapeutics, OXFORD,, ENG, United Kingdom
⁴Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

2773

BVX001, a Bispecific ADC Targeting CD7-Positive AML with Favorable Toxicity Profile, Exhibits Significant Efficacy in Primary Patient Samples and PDX-Models

Mattia Vitale, PhD¹^*, Hollie B S Griffiths, PhD²^*, Nyle Jones, PhD²^*, Meera Mistry, MSc(Eng)²^*, Jack Sangster, PhD²^*, Chloe Patterson, PhD²^*, Samuel E O'Halloran, PhD²^*, Adrian Blanco-Gomez, PhD²^*, Oliver Schon, PhD²^* and Tiffany Thorn (nee Daniels), MSc²^*

¹Bivictrix Therapeutics Plc, Nether Alderley, United Kingdom
²BiVictriX Therapeutics plc, Nether Alderley, England, United Kingdom

2774

Selective SMARCA2 Degradation Promotes Leukemic Differentiation and Synergizes with CDK9 Inhibition to Potently Induce Death in Pre-Clinical Models of Acute Myeloid Leukemia

Norman Fultang, PhD¹^*, Ashley M Schwab¹^*, Ian Johnson¹^*, Alexander Grego¹^*, Emma Filler¹^*, Carly Bachner¹^*, Jake Karwoski¹^*, Andrew Moore¹^*, Ashley Bartilomo¹^*, Anjana Agarwal¹^*, Olusola Peace Osinubi¹^*, Koichi Ito¹^*, Sarah Aminov, MSc², Srabani Sahu, MS²^*, Amit Verma, MD², Peggy A Scherle, PhD¹, Neha Bhagwat, PhD³ and Diane Heiser, PhD³^*

¹Prelude Therapeutics, Wilmington, DE
²Blood Cancer Institute, Department of Oncology, Albert Einstein College of Medicine, Bronx, NY
³Prelude Therapeutics Incorporated, Wilmington, DE

2775

Plinabulin and Selumetinib Enhance M1 Macrophage Traits and Trigger Cell Death in AML

Lucio Henrique Pinheiro, MSc^1,2^*, Isabel Weinhäuser, PhD^3,4^*, Diego A. Pereira-Martins, Ph.D.^3,5^*, Luise Araujo De Albuquerque Simoes, BS^2,6^*, Matthew Markham, PhD⁷^*, Lynn Quek, MD, Ph.D.³^*, Gerwin Huls⁴, Jan Jacob Schuringa, Prof. Dr.⁴, Stuart A Rushworth, PhD⁸ and Eduardo M. Rego, MD, PhD⁹

¹Norwich Medical School, University of East Anglia, Norwich, ENG, United Kingdom
²Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, University of São Paulo Medical School, Sao Paulo, Brazil
³Myeloid Leukaemia Genomics and Biology Group, School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
⁴Department of Experimental Hematology, University Medical Center Groningen, Groningen, Netherlands
⁵Department of Experimental Hematology, University Medical Centre Groningen, Groningen, Netherlands
⁶Department of Experimental Hematology, University Medical Center Groningen, São Paulo, SP, Brazil
⁷Norwich Medical School, University of East Anglia, Norwich, United Kingdom
⁸University of East Anglia, Norwich, United Kingdom
⁹Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, University of São Paulo Medical School, São Paulo, São Paulo, Brazil

2776

ULK1 Presents As a Therapeutic Target to Sensitize Resistant Acute Myeloid Leukemia Cells to Venetoclax

Heather Betz^1,2^* and Xiaoyan Jiang, MD, PhD^1,2

¹Terry Fox Laboratory, BC Cancer Research Centre, Vancouver, BC, Canada
²Department of Medicine, The University of British Columbia, Vancouver, BC, Canada

2777

Safety and Efficacy of a Novel Mammalian-Derived Asparaginase without Glutaminase Activity in Combination with Venetoclax for Acute Myeloid Leukemia

Dhabya Majid, BS¹^*, Zhe WANG, MD¹^*, Bin Yuan, PhD²^*, Mhd Yousuf Yassouf, PhD³^*, Amanda Schalk, PhD⁴^*, Basant T. Gamal, MS⁵^*, Qi Zhang Tatarata, MD, PhD¹^*, Jessica Lynn Root, MS⁶^*, Araceli Isabella Garza¹^*, Annie Hoai Nguyen⁷^*, Sammy Ferri-Borgogno, PhD⁵^*, Patrick K. Reville, MD, MPH¹, Arnon Lavie, PhD⁴^* and Hussein A. Abbas, MD, PhD^1,8

¹Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²The University of Texas at MD Anderson Cancer center, Houston, TX
³Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX
⁴University of Illinois, Chicago, IL
⁵University of Texas MD Anderson Cancer Center, Houston
⁶Department of Leukemia, The University of Texas MD Anderson Cancer center, Houston, TX
⁷Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston
⁸Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

2778

The Mitochondrial Unfolded Protein Response (UPR^mt) Is Upregulated in Acute Myeloid Leukemia (AML) and Inhibiting the UPR^mt Protease, LONP1, Leads to Mitochondrial Protein Aggregation and Cell Death Selectively in AML

Matthew Tcheng, BSc^1,2^*, Veronique Voisin, PhD²^*, Marcela Gronda²^*, Rose Hurren³^*, Dakai Ling²^*, Yongran Yan²^*, Lan Xin Zhang⁴^*, Yue Feng²^*, Zaynab Mamai⁵^*, Yulia Jitkova²^*, Chaitra Sarathy, PhD²^*, Andrea Arruda⁶^*, Steven M. Kornblau, MD⁷, Mark D. Minden, MD, PhD^6,8,9^* and Aaron D Schimmer, MD¹⁰

¹University Health Network, Princess Margaret Cancer Research Tower, Richmond Hill, ON, Canada
²University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada
³UHN, Princess Margaret Cancer Centre, Toronto, ON, Canada
⁴University Health Network, Princess Margaret Cancer Center, Toronto, ON, Canada
⁵University of Toronto, Toronto, ON, Canada
⁶Princess Margaret Cancer Centre / University Health Network, Toronto, ON, Canada
⁷Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁸Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
⁹Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
¹⁰Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada

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^*signifies non-member of ASH