65th ASH Annual Meeting & Exposition: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Therapeutic Implications of Leukemia Stem Cells and Differentiation in Myeloid Malignancies

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

Research, Acute Myeloid Malignancies, AML, Translational Research, Combination therapy, Diseases, Therapies, Myeloid Malignancies

Pacific Ballroom Salons 18-19 (Marriott Marquis San Diego Marina)

Moderators:

Linde A. Miles, PhD, Cincinnati Children's Hospital Medical Center and Ramy Rahme, MD, PhD,

Disclosures:

No relevant conflicts of interest to declare.

Myeloid malignancies exist on a differentiation spectrum which has been shown to have therapeutic implications. In this session, strategies to target malignant stem cell populations will be presented. Further, mechanisms regulating differentiation and how myeloid cell differentiation alters therapy response will be described.

4:30 PM

583

Stem-Cell Enriched Cellular Hierarchy of TP53 Mutant Acute Myeloid Leukemia Is Vulnerable to Targeted Protein Degradation of c-MYC

Yuki Nishida, MD, PhD¹, Edward Ayoub, PhD¹^*, Darah Scruggs, MS¹^*, Shayaun Khazaei, BS¹^*, Faryal Munir, MD, MBBS¹, Lauren B. Ostermann, BSc¹^*, Po Yee Mak¹^*, Ke Baozhen¹^*, Bing Z. Carter, PhD¹, Natalia Baran, MD, PhD, MSc², Abhishek Maiti, MD³, Vakul Mohanty, PhD⁴^*, Ken Chen, PhD⁴^*, Nicholas Navin⁵^*, Torsten Haferlach, MD, PhD⁶, Zhihua Ren, PhD⁷^*, Youzhi Tong, PhD⁷^*, Dong Chen, PhD⁷^*, Ghayas C. Issa² and Michael Andreeff, MD PhD⁸

¹Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²The University of Texas MD Anderson Cancer Center, Houston, TX
³Department of Leukemia, MD Anderson Cancer Center, Houston, TX
⁴Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
⁵Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX
⁶MLL Munich Leukemia Laboratory, Munich, Germany
⁷Kintor Pharmaceutical Ltd, Suzhou, China
⁸Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX

4:45 PM

584

Myelodysplastic Syndrome Hematopoietic Stem Cells Can Undergo Differentiation Trajectory Rewiring to Escape Venetoclax Vulnerability

Juan Jose Rodriguez Sevilla¹^*, Irene Ganan-Gomez, PhD, MSc¹^*, Feiyang Ma²^*, Kelly S. Chien, MD³, Guillermo Montalban-Bravo, MD³, Rashmi Kanagal-Shamanna, MD⁴, Sanam Loghavi, MD⁴, Vera Adema⁵^*, Natthakan Thongon, PhD¹, Alexandre Bazinet, MD⁶^*, Guillermo Garcia-Manero, MD⁷ and Simona Colla, PhD⁸

¹Leukemia, MD Anderson Cancer Center, Houston, TX
²University of Michigan, Ann Arbor, MI
³Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁴Hematopathology, MD Anderson Cancer Center, Houston, TX
⁵Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houst, Houston, TX
⁶Department of Leukemia, MD Anderson Cancer Center, Houston, TX
⁷The University of Texas MD Anderson Cancer Center, Houston, TX
⁸MD Anderson Cancer Center, HOUSTON, TX

5:00 PM

585

Polyamines Are Required for AML LSC Function through Their Role in Regulating eIF5A Dependent Protein Synthesis

Vincent Rondeau, PhD¹, Rachel Culp-Hill, PhD²^*, Julie A Reisz, PhD²^*, Duhan Yendi¹^*, Aarushi Gupta³^*, Jacob Berman¹^*, Cristiana O'Brien³^*, Tianyi Ling³, Aleksandra Bourdine³^*, Mary Shi¹^*, Jonathan St-Germain, PhD⁴^*, Soheil Jahangiri, PhD^1,3^*, Anastasia N. Tikhonova, PhD^1,3, Andrea Arruda⁵^*, Mark D. Minden^1,3^*, Brian Raught, PhD^3,4^*, Angelo D'Alessandro, PhD² and Courtney L Jones, PhD^3,6

¹Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
²Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO
³Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
⁴University Health Network, Princess Margaret Cancer Centre, Toronto, ON, Canada
⁵Princess Margaret Cancer Centre, University Health Network, Toronto, Canada
⁶Princess Margaret Cancer Centre, University Health NetworkCin, Toronto, ON, Canada

5:15 PM

586

IL1RAP-Specific T Cell Engager (TCE) Antibody Efficiently Depletes Acute Myeloid Leukemia (AML) Leukemic Stem Cells (LSCs)

Yi Zhang^1,2^*, Miso Park³^*, Bin Zhang²^*, Lucy Y. Ghoda, PhD²^*, Dandan Zhao², Melissa Valerio²^*, Ebtesam Nafie²^*, Xubo Gong^2,4^*, Fang Chen²^*, Yongfang Xu²^*, Katrina Estrella²^*, Kaito Harada²^*, Shawn Sharkas²^*, Hyunjun Kang, PhD²^*, Dinh Hoa Hoang²^*, Le Xuan Truong Nguyen, PhD²^*, Stephen J. Forman, MD, FACP⁵, Idoroenyi Amanam, MD², Flavia Pichiorri⁶, Jie Jin¹, John C. Williams³^* and Guido Marcucci, MD²

¹Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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 Cancer Biology and Molecular Medicine, Beckman Research Institute, City of Hope, Duarte, CA
⁴Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
⁵Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope National Medical Center, Duarte, CA
⁶Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA

5:30 PM

587

Decoding the Epigenetic Drivers of Menin-MLL Inhibitor Resistance in KMT2A-Rearranged Acute Myeloid Leukemia

Xinyue Zhou, BPharm^1,2^*, Lixia Zhang^2,3^*, Sajesan Aryal^1,2, Steven Moreira⁴^*, Virginia Veasey^2,3^*, Kristin J. Hope^4,5 and Rui Lu, PhD^2,6

¹Department of Medicine, Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL
²O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL
³Department of Medicine, Division of Hematology/Oncology, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL
⁴Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
⁵Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
⁶Department of Medicine, Division of Hematology/Oncology, University of Alabama At Birmingham, Birmingham, AL

5:45 PM

588

Targeting Mitochondrial Calcium Uptake to Eradicate Venetoclax-Resistant Acute Myeloid Leukemia Stem Cells

Anagha Inguva Sheth, BSc¹, Krysta Engel, PhD¹^*, Hunter Tolison, BS¹^*, Mark Jordan Althoff, PhD¹^*, Anna Krug²^*, Maria L Amaya, MD, PhD^3,4, Shanshan Pei, PhD⁵^*, Tracy Young¹^*, Sweta B Patel, PhD¹^*, Mohd Minhajuddin, PhD¹^*, Regan Miller, MS¹^*, Ian Shelton, BA¹^*, Ana Vujovic, PhD¹^*, Courtney L Jones, PhD⁶, Austin E Gillen, PhD¹^*, Monica Ransom, PhD¹^*, Sarah Staggs, PhD¹^*, Clayton Smith, MD⁷, Daniel A. Pollyea, MD, MS⁸, Brett M Stevens, PhD, BS¹^* and Craig T. Jordan, PhD¹

¹University of Colorado School of Medicine, Aurora, CO
²University of Colorado Anschutz Medical Campus, Aurora, CO
³Division of Hematology, University of Colorado, Aurora, CO
⁴Rocky Mountain Regional VA Medical Center, Aurora, CO
⁵Liangzhu Laboratory, Zhejiang University, hangzhou, CO, China
⁶Princess Margaret Cancer Centre, University Health NetworkCin, Toronto, ON, Canada
⁷CU Innovations, University of Colorado, Aurora, CO
⁸Division of Hematology, University of Colorado School of Medicine, Aurora, CO

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^*signifies non-member of ASH

604.O2.6 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Therapeutic Implications of Leukemia Stem Cells and Differentiation in Myeloid Malignancies