57th ASH Annual Meeting and Exposition (December 5-8, 2015): 605. Molecular Pharmacology, Drug Resistance

Molecular Pharmacology, Drug Resistance – Lymphoid and Other Diseases Oral and Poster Abstracts
Poster

Hall A, Level 2 (Orange County Convention Center)

The Wee1 Inhibitor, MK-1775, Sensitizes Leukemic Cells to Different Antineoplastic Drugs Interfering with DNA Damage Response Pathway

Andrea Ghelli Luserna Di Rora¹^*, Ilaria Iacobucci, PhD²^*, Neil Beeharry³^*, Simona Soverini⁴, Cristina Papayannidis, MD, PhD⁵, Giovanni Martinelli, MD, PhD⁵ and Timothy J Yen³^*

¹DIMES, Department of Hematology and Medical Sciences “L. and A. Seràgnoli”, University of Bologna, Bologna, Italy
²"Seràgnoli" Institute of Hematology, University of Bologna, Bologna, Italy
³Cancer Biology Program, Fox Chase cancer center, Philadelphia
⁴Institute of Hematology, S.Orsola-Malpighi University Hospital, Bologna, Italy
⁵Bologna University School of Medicine, Bologna, Italy

1277

Targeting BCL6-Mediated Resistance to BCR-ABL Targeted Tyrosine Kinase Inhibitors (TKIs) in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) through the Addition of Histone Deacetylase (HDAC) Inhibitors

Gordon Cohen, MD, MPH¹^*, Colleen E. Annesley, MD², Rachel E. Rau, MD³, Shannon Kelley²^*, Daniel Magoon²^* and Patrick Brown, MD²

¹Pediatric Hematology/Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
²Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
³Department of Pediatrics, Baylor College of Medicine, Houston, TX

1278

Proteasome Inhibitor-Adapted Myeloma Cells That Lack Proteasome Gene Mutations Resist Highly Efficient Proteasome Inhibition and Show Proteomic Alterations That Suggest Complex Metabolic Changes

Lenka Besse, PhD¹^*, Guillem Soriano²^*, Nan Li²^*, Andrej Besse¹^*, Marianne Kraus¹^*, Juergen Bader¹^*, Tobias Christian Silzle, MD¹^*, Nico Meeuwenoord²^*, Hans den Dulk²^*, Herman S Overkleeft²^*, Bogdan Florea²^* and Christoph Driessen, MD¹

¹Kantonsspital St.Gallen, St.Gallen, Switzerland
²Leiden Institute of Chemistry and Netherlands Proteomics Centre, Leiden University, Leiden, Netherlands

1279

In Silico Modeling of Oncogenic Drivers in Waldenstrom Macroglobulinemia to Assess Additional Therapeutic Targets within the BCR Signaling Pathway Identifies MEK1/2 As a Target: Potential Therapeutic Role of Binimetinib

Aneel Paulus, MD, MS¹, Sharoon Akhtar, MPhil²^*, Shireen Vali³^*, Ansu Kumar⁴^*, Neeraj Kumar Singh⁴^*, Shahabuddin Usmani⁵^*, Himanshu Grover⁶^*, Taher Abbasi⁷^* and Asher Alban Chanan-Khan, MD⁸

¹Cancer Biology, Mayo Clinic, Jacksonville, FL
²Department of Cancer Biology, Mayo Clinic, Jacksonville, FL
³Cellworks Group Inc., 2033 Gateway Place Suite 500, San Jose, CA
⁴Cellworks Group, Inc., San Jose, CA
⁵Cellworks Research India Ltd, Whitefield, India
⁶Cellworks Research India Limited, Whitefield, India
⁷Cellworks Research India Ltd., Bangalore, India
⁸Division of Hematology & Oncology, Mayo Clinic, Jacksonville, FL

1280

Translational Focus on Targeting HDAC6 with Ricolinostat Confirms Potent Activity in Preclinical Models of Lymphoma and a Favorable Toxicity Profile in Patients with Relapsed or Refractory Lymphoma

Jennifer E Amengual, MD¹, Lichtenstein Renee¹^*, Celeste Rojas¹^*, Kelly Zullo, MS²^*, Maximilian Lombardo¹^*, Emily Lichtenstein, RN¹^*, Ellen Neylon, NP³^*, Changchun Deng, MD, PhD², Ahmed Sawas, MD¹, Bijal D Shah⁴, Catherine Wheeler, MD⁵^*, Simon S Jones, PhD⁵^* and Owen A. O'Connor, MD, PhD¹

¹Center for Lymphoid Malignancies, Columbia University Medical Center, New York, NY
²Center for Lymphoid Malignancies, Department of Medicine, Columbia University Medical Center, New York, NY
³Center for Lymphoid Malignancies at Columbia University Medical Center, New York, NY
⁴H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
⁵Acetylon Pharmaceuticals, Inc., Boston

1281

Population Pharmacokinetics of Erwinia Asparaginase in Pediatric ALL Patients

Sebastiaan D.T. Sassen, PharmD¹^*, Ron A.A. Mathôt, PharmD, PhD²^*, Rob Pieters, MD, PhD³, Valerie de Haas, MD, PhD⁴^*, Gertjan JL Kaspers, MD, PhD⁵, Cor van den Bos, MD PhD⁶^*, Wim JE Tissing, MD, PhD⁷^*, Maroeska D.W.M. te Loo, MD, PhD⁸, Marc B Bierings, MD PhD⁹, Wouter J.W. Kollen, MD, PhD¹⁰^*, Christian M. Zwaan, MD, PhD¹¹ and Inge M. van der Sluis, MD, PhD¹²

¹Pediatric Oncology, Erasmus MC - Sophia Children's Hospital, Rotterdam, Netherlands
²Clinical Pharmacology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
³Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands
⁴Dutch Childhood Oncology Group (DCOG), The Hague, Netherlands
⁵Pediatric Hematology Oncology, VU University Medical Center, Amsterdam, Netherlands
⁶Department of Pediatric Oncology, Academic Medical Center, Amsterdam, Netherlands
⁷Department of Paediatric Oncology, University Medical Center Groningen, Groningen, Netherlands
⁸Pediatric Hemato-Oncology, UMCN St Radboud, Nijmegen, Netherlands
⁹Department of Hematology and Immunology, Wilhelmina Children's Hospital, Utrecht, Netherlands
¹⁰Department of Pediatric Immunology, Hemato-Oncology and Stem Cell Transplantation, Leiden University Medical Center, Leiden, Netherlands
¹¹Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands
¹²Department of Pediatric Oncology/ Hematology, Erasmus MC - Sophia Children's Hospital, Rotterdam, Netherlands

1282

Targeting Epigenetic Operations with HDAC Inhibitor and Hypomethylating Drugs in Combination Exhibit Synergy in Preclinical and Clinical Experiences in Drug Resistant T-Cell Lymphoma (TCL): A Translational Focus on Doublet Development

Owen A. O'Connor, MD, PhD¹, Kelly Zullo, MS²^*, Enrica Marchi, MD, PhD², Changchun Deng, MD, PhD², Ahmed Sawas, MD², Donald Steven Colbourn, MD³^*, Celeste Rojas²^*, Renee Lichtenstein⁴^*, Ellen Neylon, NP⁵^*, Emily Lichtenstein, RN²^*, Michael Smith, RN²^*, Luigi Scotto, PhD¹^* and Jennifer E Amengual, MD²

¹Center for Lymphoid Malignancies, Department of Medicine, Columbia University Medical Center, New York, NY
²Center for Lymphoid Malignancies, Columbia University Medical Center, New York, NY
³Center for Lymphoid Malignancies, Columbia University Medical Center, NY, NY
⁴Center for Lymphoid Malignancies, Department of Medicine, Columbia University Medical Center, New York
⁵Center for Lymphoid Malignancies at Columbia University Medical Center, New York, NY

1283

Activation of Simultaneous Apoptosis and Necroptosis to Eradicate Drug Resistant Leukemia

Scott McComb, PhD¹^*, Julia Aguadé-Gorgorió¹^*, Blerim Marovca¹^*, Lena Harder¹^*, Gunnar Cario²^*, Cornelia Eckert³^*, Martin Schrappe, MD, PhD², Martin Stanulla, MD⁴^*, Arend von Stackelberg, MD⁵, Jean-Pierre Bourquin, MD, PhD¹ and Beat Bornhauser, PhD¹^*

¹Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland
²Dept. of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
³Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin, Berlin, Germany
⁴Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany
⁵Department of Pediatric Oncology and Hematology, Charité - University Hospital Berlin, Berlin, Germany

1284

Lipid Addiction of Diffuse Large B-Cell Lymphoma (DLBCL): Fatty Acid Synthase (FASN) and PI3K Dependent Cell Death Identifies a Novel Therapeutic Paradigm

Ravi Dashnamoorthy, PhD¹, Afshin Beheshti, PhD¹^*, Nassera Abermil, MS, PharmD²^*, Frederick Lansigan, MD³, William Kinlaw, MD⁴^*, Ron Gartenhaus, MD⁵, Graham Jones, PhD, DSc⁶^*, Lynn Hlatky, PhD²^* and Andrew M. Evens, DO, MSc⁷

¹Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA
²Tufts Medical Center, Boston
³Hematology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
⁴Endocrinology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
⁵Greenebaum Cancer Center, University of Maryland, Baltimore, MD
⁶Department of Chemistry, Northeastern University, Boston, MA
⁷Tufts Medical Center Cancer Center, Boston, MA

1285

L-Asparaginase More Effectively Targets Leukemic Cells with Low Glycolytic Activity

Simcikova Marketa¹^*, Alena Pecinova²^*, Ivana Hermanova¹^*, David Pajuelo Reguera¹^*, Katerina Rejlova¹^*, Marketa Zaliova³, Jan Stuchly³^*, Tomas Mracek²^*, Jan Trka³ and Julia Starkova³^*

¹CLIP-Childhood Leukaemia Investigation Prague, Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
²Department of Bioenergetics, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic
³CLIP- Childhood Leukaemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic

1286

Hypoxia Induces Pgp-Mediated Carfilzomib Resistance in Multiple Myeloma Cells and HIF Inhibition Significantly Enhances Sensitivity and Response to Carfilzomib In Vivo

Barbara Muz, PhD, MSc¹, Joseph Abraham²^*, Feda Azab, BPharm³^*, Pilar De La Puente, PhD¹, Nicholas Potter⁴^*, Benjamin Minch⁵^*, Farideh Ordikhani⁶^*, Noha Salama⁵^* and Abdel Kareem Azab, BPharm, PhD¹

¹Department of Radiation Oncology, Cancer Biology Division, Washington University in Saint Louis School of Medicine, Saint Louis, MO
²St Louis College of Pharmacy, Saint Louis, MO
³Washington University In St. Louis, Saint Louis, MO
⁴St. Louis College of Pharmacy, Saint Louis, MO
⁵St Louis College of Pharmacy, Saint Louis
⁶Radiation Oncology, Washington Univeristy in St. Louis, Saint Louis

1287

Gli1 Inhibitor GANT61 Exhibits Antitumor Efficacy in T-Cell Lymphoma Cells through Down-Regulation of p-STAT3 and SOCS3 Pathways

Lingyun Geng, MD^*, Xiangxiang Zhou, MD^*, Xinyu Li, MD^*, Kang Lu, PhD^*, Peipei Li, PhD^* and Xin Wang, MD, PhD

Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China

1288

FTY720 (Fingolimod) Targets the Sphingolipid Pathway and Induces Autophagy-Related Apoptosis in Human Natural Killer Large Granular Lymphocyte Leukemia

Francis Roland LeBlanc, B.S.¹^*, Hong-Gang Wang, MD, PhD²^*, David J. Feith, Ph.D.³^* and Thomas P. Loughran Jr., MD⁴

¹Penn State Hershey Cancer Institute, Hershey, PA
²Department of Pharmacology, Penn State Hershey Cancer Institute, Hershey, PA
³Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA
⁴Department of Medicine, University of Virginia, Charlottesville, VA

1289

Targeting the Tumor Evasion Interaction of NKG2A and Its Ligand HLA-E Increases Natural-Killer Cell Activity in Chronic Lymphocytic Leukemia

Emily McWilliams¹^*, Jennifer M Mele, MS¹^*, Faraz Fiazuddin¹^*, Carolyn Cheney, BS²^*, Natarajan Muthusamy, DVM, Ph.D.³ and Farrukh T. Awan, MD, MS³

¹The Ohio State University, Columbus, OH
²Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH
³Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH

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^*signifies non-member of ASH

605.P1.46 605. Molecular Pharmacology, Drug Resistance – Lymphoid and Other Diseases: Poster I