62nd ASH Annual Meeting and Exposition: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster I

Oral and Poster Abstracts
Poster

AML, apoptosis, Biological, bone marrow, Diseases, Non-Biological, chemical interactions, Combinations, Therapies, cellular interactions, chemotherapy, Biological Processes, DNA damage, cell expansion, Technology and Procedures, gene editing, Lymphoid Malignancies, Clinically relevant, Myeloid Malignancies, pharmacology, flow cytometry, mass cytometry, NGS, metabolomics, microenvironment, pathways, signal transduction

956

Co-Targeting MCL-1 and BCL-2 Is Highly Synergistic in BH3 Mimetic- and Venetoclax/Hypomethylating Agent-Resistant and TP53 Mutated AML

Bing Z Carter, PhD¹, Po Yee Mak¹^*, Wenjing Tao¹^*, Vivian Ruvolo, MS¹^*, Xuan Zhang, PhD¹^*, Yuki Nishida, MD, PhD¹, Steven M. Kornblau, MD¹, Paul Hughes²^*, Xiaoyue Chen²^*, PK Morrow³^* and Michael Andreeff, MD, PhD¹

¹Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Oncology Research, Amgen Inc., Thousand Oaks, CA
³Amgen Inc., Thousand Oaks, CA

957

CXCL12 Knock-out Enhances Leukemia Stem Cell Response to Combination Chemotherapy Plus Tyrosine Kinase Inhibition in Flt3-ITD Acute Myeloid Leukemia

Nick R Anderson, BS¹, Hui Li, BS¹^*, Mason W Harris¹^*, Shaowei Qiu, MD¹^*, Amanda K Mullen¹^*, Andrew J Paterson, PhD²^* and Ravi Bhatia, MD¹

¹Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL
²Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL

958

The Novel Dihydroorotate Dehydrogenase (DHODH) Inhibitor PTC299 Inhibit De Novo Pyrimidine Synthesis with Broad Anti-Leukemic Activity Against Acute Myeloid Leukemia

Sujan Piya, PhD¹, Marla Weetall, PhD²^*, Josephine Sheedy, BS, MSc²^*, Balmiki Ray, PhD³^*, Huaxian Ma, MS⁴^*, Kensuke Kojima, MD, PhD⁵, Vivian Ruvolo, MS⁶^*, Mahesh Basyal, BS⁶^*, Marina Konopleva, MD, PhD⁴, Michael Andreeff, MD, PhD⁶ and Gautam Borthakur, MD⁷

¹Department of Leukemia, The University of Texas MD Anderson Cancer Center, Pearland, TX
²PTC Therapeutics Inc., South Plainfield, NJ
³PTC Therapeutics Inc., South Plainsfield, NJ
⁴Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁵Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
⁶Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁷Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX

959

“Triple” Combination of Targeting Methyltransferase, BCL-2 and PD-1 Facilitates Therapeutic Responses in Acute Myeloid Leukemia (AML)

Zhihong Zeng, MD¹^*, Shelley Herbrich, PhD¹, Tianyu Cai, PhD¹^*, Antonio Cavazos, MSc¹^*, Taylor Manzella¹^*, Helen Ma, MS¹^*, Vinitha Mary Kuruvilla, MSc¹^*, Kala Hayes¹^*, Jairo A. Matthews¹^*, Courtney D. DiNardo, MD, MSc², Naval Daver, MD¹ and Marina Konopleva, MD, PhD³

¹Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
²Department of Leukemia, UT MD Anderson Cancer Center, Houston, TX
³Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX

960

The Direct Interactions with Bone Marrow Microenvironment Confer Resistance to the Inhibition of Oxidative Phosphorylation in AML

Yoko Tabe, MD, PhD^1,2,3, Kaori Saito¹^*, Kotoko Yamatani, MD^1,4^*, Haeun Yang¹^*, Rodrigo Jacamo, PhD⁵^*, Helen Ma, MS⁶^*, Vivian Ruvolo, MS⁵^*, Qi Zhang, PhD⁶^*, Vinitha Mary Kuruvilla, MSc⁶^*, Natalia Baran, PhD, MD⁷, Junichi Imoto⁸^*, Kazuho Ikeo, PhD⁹^*, Koya Suzuki, PhD^1,10^*, Takashi Miida, MD, PhD¹^*, Michael Andreeff, MD, PhD⁵, Christopher P Vellano¹¹^*, Joseph R Marszalek, PhD¹²^* and Marina Konopleva, MD, PhD¹³

¹Department of Clinical Laboratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan
²Section of Molecular Hematology and Therapy, Department of Leukemia, MD Anderson Cancer Center, Houston, TX
³Department of Next Generation Hematology Laboratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
⁴Research Fellow of the Japan Society for the Promotion of Science, Tokyo, Japan
⁵Section of Molecular Hematology and Therapy, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁶Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁷Department of Leukemia, MD Anderson Cancer Center, Houston, TX
⁸National Institute of Genetics, Shizuoka, Japan
⁹Centers for Information Biology, National Institute of Genetics, Shizuoka, Japan
¹⁰Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan
¹¹TRACTION, The University of Texas MD Anderson Cancer Center, Houston
¹²Institute for Applied Cancer Science & Center for Co-Clinical Trials, The University of Texas MD Anderson Cancer Center, Houston, TX
¹³Department of Leukemia, University of Texas, MD Anderson Cancer Center, Houston, TX

961

Pyruvate Dehydrogenase Inhibition Leads to Decreased Glycolysis and Increased Reliance on Gluconeogenesis in Acute Myeloid Leukemia

Rebecca G. Anderson, B.S.¹^*, Kristin M. Pladna, M.S.¹^*, Nathaniel J Schramm, MS¹^* and Timothy S. Pardee, MD, PhD²

¹Comprehensive Cancer Center of Wake Forest Baptist Health, Winston-Salem, NC
²Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Winston Salem, NC

962

Anlotinib Induced Apoptosis and Regulated the Chemosensitivity and Immune-Related Properties of Leukemia Stem Cells By Inhibiting JAK2-STAT3/5 Signaling

Long Liu, MD, PhD¹^*, Long Yue Jiang²^* and Bing Xu, MD, PhD¹^*

¹Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China
²Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, China

963

Co-Occurring Mutation Clusters Predict Drug Sensitivity in Acute Myeloid Leukemia

Guangrong Qin, PhD¹^*, Shmulevich Ilya, PhD¹^*, Taek-Kyun Kim, PhD¹^*, Bahar Tercan, PhD¹^*, Timothy J Martins, PhD²^*, Jin Dai, PhD³^*, Sylvia Chien⁴^*, Andrew Carson, PhD⁵^*, Bradley Patay, MD⁵^*, Elihu H. Estey, MD^3,6,7, Lawrence A. Loeb, MD, PhD⁸^*, Raymond J. Monnat, MD, PhD⁹^* and Pamela S. Becker, MD, PhD^7,10,11

¹Institute for Systems Biology, Seattle, WA
²Institute for Stem Cell and Regenerative Medicine/Department of Medicine, University of Washington, Seattle, WA
³Department of Medicine, University of Washington, Seattle, WA
⁴Institute for Stem Cell and Regenerative Medicine/Division of Hematology/Department of medicine, University of Washington, Seattle, WA
⁵Invivoscribe Inc., San Diego, CA
⁶Seattle Cancer Care Alliance, Seattle, WA
⁷Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
⁸Pathology/Department of medicine, University of Washington, Seattle, WA
⁹Department of Pathology and Genome Sciences, University of Washington, Seattle, WA
¹⁰Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA
¹¹Division of Hematology and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA

964

RNA Cytosine Methyltransferases NSUN1 and NSUN2 Mediate the Lineage-Associated Resistance to Venetoclax in Leukemia

Shaun Wood, B.A. & M.S.¹^*, Amber Willbanks, B.A.¹^* and Jason Xiaojun Cheng, MD, PhD^1,2

¹Pathology, University of Chicago, Chicago, IL
²University of Chicago Comprehensive Cancer Center, Chicago, IL

965

CRISPR/Cas9 Chemogenetic Profiling Identifies Candidate Biomarker Genes That Modulate Sensitivity to Selinexor

Bert Kwanten, MSc¹^*, Yosef Landesman, PhD²^* and Dirk Daelemans³^*

¹KU Leuven, Leuven, Belgium
²Karyopharm Therapeutics, Newton, MA
³REGA- KU Leuven, Leuven, Belgium

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^*signifies non-member of ASH

604.P1.27 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Poster I