57th ASH Annual Meeting and Exposition (December 5-8, 2015): 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster I

Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy Oral and Poster Abstracts
Poster

Hall A, Level 2 (Orange County Convention Center)

Tuning T Cell Affinity Improves Efficacy and Safety of Anti-CD38 × Anti-CD3 Bispecific Antibodies in Monkeys - a Potential Therapy for Multiple Myeloma

Gregory L. Moore, PhD^*, Sung-Hyung Lee, PhD^*, Suzanne Schubbert, PhD^*, Yvonne Miranda, MS^*, Rumana Rashid, PhD^*, Erik Pong, BS^*, Sheryl Phung, MS^*, Emily W. Chan, BS^*, Hsing Chen, MS^*, Nancy Endo, BS^*, Maria C. Ardila, BS^*, Matthew J. Bernett, PhD^*, Seung Chu, PhD^*, Irene W.L. Leung, PhD^*, Umesh Muchhal, PhD^*, Christine Bonzon, PhD^*, David E Szymkowski, PhD^* and John Desjarlais, PhD^*

Xencor, Inc., Monrovia, CA

1799

Soluble Bcma in Myeloma Serum Binds Its Ligands BAFF and Prevents Normal Antibody Production in Multiple Myeloma Patients

Eric Sanchez, BA¹^*, Abigail Gillespie, BS¹^*, Nika Manik Harutyunyan²^*, George Tang, PhD¹^*, Jillian Gottlieb²^*, Suzie Vardanyan, MS¹^*, Mingjie Li, BS¹^*, Claudia Andreu-Vieyra³^*, Michael Ghermezi³^*, Cathy Wang, BS¹^*, Joseph Ben-Zvi³^*, Gigi Garzio³^*, Haiming Chen, MD, PhD¹ and James Berenson, MD¹

¹Institute for Myeloma & Bone Cancer Research, West Hollywood, CA
²Institute for Myeloma and Bone Cancer Research, Hollywood, CA
³Institute for Myeloma and Bone Cancer Research, Hollywood

1800

Drug Design for Overcoming High-Risk Myeloma and Identification of Novel Binding Proteins to Immune-Modulatory Drugs

Masashi Hozumi¹^*, Daiju Ichikawa, PhD¹^*, Maiko Matsushita, MD, PhD¹^*, Eriko Kamiyama¹^*, Hiroshi Yanagawa, PhD^1,2^*, Noriko Tabata, PhD²^*, Shotaro Kitabatake¹^*, Arimi Ueda¹^*, Takashi Yamaguchi¹^*, Mariko Sato¹^* and Yutaka Hattori, MD, PhD¹

¹Faculty of Pharmacy, Keio University, Tokyo, Japan
²Faculty of Science and Technology, Keio University, Yokohama, Japan

1801

Mechanisms Underlying the Synergistic Interaction of Filanesib with Pomalidomide and Dexamethasone (FPD) in Multiple Myeloma

Susana Hernández-García¹^*, Laura San-Segundo¹^*, Lorena González-Méndez¹^*, Montserrat Martín-Sánchez¹^*, Luis A Corchete¹^*, Teresa Paíno¹^*, Ana Alicia López-Iglesias¹^*, Esperanza Macarena Algarín¹^*, Mercedes Garayoa¹^*, Brian Tunquist², Norma C Gutierrez¹^*, Maria-Victoria Mateos, MD, PhD¹ and Enrique M Ocio¹^*

¹Complejo Asistencial Universitario de Salamanca (IBSAL) y Centro de Investigación del Cáncer (IBMCC-CSIC). Universidad de Salamanca, Salamanca, Spain
²Array Biopharma, Boulder, CO

1802

Metabolomic, Proteomic and Genomic Profiling Identifies Biomarakers of Sensitivity to Glutaminase Inhibitor CB-839 in Multiple Myeloma

Andrew L MacKinnon, Ph.D.^*, Mark Bennett, PhD, Matt Gross, B.S.^*, Julie Janes, M.S.^*, Weiqin Li, Ph.D.^*, Mirna Rodriquez, B.S.^*, Tracy Wang, BS^*, Winter Zhang, B.S.^* and Francesco Parlati, PhD

Calithera Biosciences, South San Francisco, CA

1803

Predicting Non-Responders to Immunotherapy Treatments through Simulation of NGS Information

Kim A. Brogden¹^*, Carol L. Fischer¹^*, Amber M. Bates¹^*, Emily A. Lanzel²^*, Maria Paula Gomez Hernandez¹^*, Christopher N. Treinen¹^*, Erica N. Recker¹^*, Prashant R. Nair³^*, Karthik Sundara³^*, Vishwas Joseph³^*, Taher Abbasi^3,4^* and Shireen Vali^3,4^*

¹Dows Institute for Dental Research, University of Iowa, Iowa City, IA
²Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA
³Cellworks Research India Ltd., Bangalore, India
⁴Cellworks Group Inc., 2033 Gateway Place Suite 500, San Jose, CA

1804

Targeting Neddylation to Overcome Drug Resistance in Multiple Myeloma

Gregory S Thomas, PhD¹^*, Junwei Huang, MD²^*, Yi Zhou, PhD³^*, Zhimin Gu, PhD⁴^*, Ye Yang, PhD⁵, Hongwei Xu⁶^*, Guido J Tricot, MD, PhD⁷ and Fenghuang Zhan, MD, PhD⁴

¹Division of Hematology, Oncology, and Blood and Marrow Transplantation, University of Iowa, Iowa City, IA
²School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
³University of Iowa, Iowa City
⁴Department of Internal Medicine, University of Iowa, Iowa City, IA
⁵Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA
⁶Department of Internal Medicine, University of Iowa, Iowa city, IA
⁷Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA

1805

E-Selectin Ligand Expression Increases with Progression of Myeloma and Induces Drug Resistance in a Murine Transplant Model, Which Is Overcome By the Glycomimetic E-Selectin Antagonist, GMI-1271

Alessandro Natoni, PhD¹^*, Theodore A.G. Smith, Ph.D.²^*, Niamh Keane, MB, MRCP³^*, Silvia C. Locatelli-Hoops, Ph.D.²^*, Isabela Oliva²^*, William E. Fogler, Ph.D.²^*, John L. Magnani, PhD² and Michael O'Dwyer, MD⁴

¹Biosciences, National University of Ireland Galway, Galway, Ireland
²GlycoMimetics, Inc., Rockville, MD
³National University of Ireland Galway, Galway, Ireland
⁴University of Ireland Galway, Galway, Ireland

1806

The Composition and Clinical Impact of Focal Lesions and Their Impact on the Microenvironment in Myeloma

Shmuel Yaccoby, PhD¹, Joshua Epstein, DSc¹, Sarah K. Johnson, PhD¹, Pingping Qu, PhD²^*, Frits van Rhee, MD, PhD¹, Yogesh Jethava, MB, MRCP, MD, FRCPath¹, Caleb K. Stein, MS¹^*, Emily Hansen²^*, Alan Mitchell²^*, Maurizio Zangari, MD¹^*, Christoph Heuck, MD¹, Rashid Z Khan, MD¹^*, Xenofon Papanikolaou, MD¹^*, Faith E Davies, MD¹, Antje Hoering, Ph.D.²^*, John Crowley, PhD², Niels Weinhold, PhD¹^*, Bart Barlogie, MD, PhD¹ and Gareth J Morgan, MD PhD¹

¹Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR
²Cancer Research and Biostatistics, Seattle, WA

1807

Small Molecule Inhibition of SIRT Activity: A Novel Therapeutic Approach for Refractory Multiple Myeloma

Steffan T. Nawrocki, Ph.D.¹, Claudia M. Espitia²^*, Valeria Visconte, PhD³^*, Yingchun Han, MD³^*, Kevin R. Kelly, MD, PhD⁴ and Jennifer S. Carew, Ph.D.³

¹CTRC Institute for Drug Development, University of Texas Health Science Center at San Antonio, San Antonio, TX
²University of Texas Health Science Center at San Antonio, CTRC Institute for Drug Development, San Antonio
³Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
⁴University of Southern California Keck School of Medicine, Los Angeles, CA

1808

Melphalan Affects Genes Critical for Myeloma Survival, Homing, and Response to Cytokines and Chemokines

Shmuel Yaccoby¹, Joshua Epstein, DSc¹, Pingping Qu, PhD²^*, Frits van Rhee, MD, PhD¹, Maurizio Zangari, MD¹, Christoph Heuck, MD¹, Faith E Davies, MD¹, Alan Mitchell²^*, Antje Hoering, Ph.D.²^*, John Crowley, PhD², Bart Barlogie, MD, PhD¹ and Gareth J Morgan, MD PhD¹

¹Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR
²Cancer Research and Biostatistics, Seattle, WA

1809

CD26 Is a Novel Target for the Treatment of Tumor Progression and Its Related Osteolytic Bone Disease in Multiple Myeloma

Hiroko Nishida, M.D., Ph.D.¹, Hiroko Madokoro¹^*, Hiroshi Suzuki¹^*, Mutsumi Hayashi, M.D., Ph.D.¹^*, Chikao Morimoto, M.D., Ph.D.²^*, Michiie Sakamoto, M.D., Ph.D.¹^* and Taketo Yamada, M.D., Ph.D.^1,3^*

¹Department of Pathology, Keio University, School of Medicine, Tokyo, Japan
²Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
³Department of Pathology, Saitama Medical University, Faculty of Medicine, Saitama, Japan

1810

APRIL/B Cell Maturation Antigen (BCMA) Signaling Cascades Promote Human Multiple Myeloma Growth and Mediate Immunosuppression in the Bone Marrow Microenvironment Via IL-10, TGF-b, and PD-L1

Yu-Tzu Tai, PhD¹, Chirag Acharya, MD²^*, Gang An, MD.PhD¹^*, Michele Moschetta, MD³^*, Mike Zhong, BS⁴^*, Xiaoyan Feng, MD⁵^*, Hans van Eenennaam, PhD⁶^*, Andrea van Elsas, PhD⁶^*, Lugui Qiu, MD, PhD⁷, Nikhil C. Munshi, MD¹ and Kenneth C Anderson, MD⁸

¹Harvard Medical School, the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA
²Harvard Medical School, the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Boston, MA
³Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
⁴the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA
⁵State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
⁶BioNovion, Oss 5342, Netherlands
⁷State Key Lab of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China
⁸The Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

1811

Targeting 19S-Proteasome Deubiquitinase Rpn11/POH1/PSMD14 in Multiple Myeloma

Yan Song, Ph.D¹^*, Arghya Ray, PhD¹, Deepika Sharma DAS, PhD¹^*, Dharminder Chauhan, PhD¹ and Kenneth C Anderson, MD²

¹The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
²LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

1812

Exquisite Sensitivity of Plasma Cell Malignancies to a Novel Nucleoside Analog Is Mediated By Overexpressed Adenosine Kinase

Utthara Nayar¹^*, Jouliana Sadek¹^*, Jonathan B Reichel¹^*, David Bunn²^*, Denise Hernandez-Hopkins¹^*, Peter Barelli³^*, Michelle Sahai⁴^*, Jennifer Totonchy¹^*, Sei Shizuko⁵^*, Robert Shoemaker⁶^*, David Warren³^*, Olivier Elemento⁴^*, Kenneth Kaye⁷ and Ethel Cesarman¹

¹Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY
²Gateways Laboratory Program, Weill Cornell Medical College, New York, NY
³Department of Biochemistry, Weill Cornell Medical College, New York, NY
⁴Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY
⁵Viral Vector Toxicology Section, LHTP, SAIC-Frederick, National Cancer Institute at Frederick, frederick, MD
⁶Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, Frederick, MD
⁷Department of Medicine, Brigham and Women's Hospital, Boston, MA

1813

Targeting Deubiquitylating Enzyme USP1 in Multiple Myeloma

Deepika Sharma Das, PhD¹^*, Yan Song, Ph.D¹^*, Arghya Ray, PhD¹, Paul Richardson, MD¹, Dharminder Chauhan, PhD¹ and Kenneth C Anderson, MD²

1814

Proteomic Characterization of Circulating Extracellular Vesicles Identifies Novel Serum Myeloma Associated Markers

David Ciarlariello¹^*, Sean Harshman¹^*, Alessandro Canella¹^*, Erinn Hade¹^*, Alberto Rocci, MD²^*, Antonio Palumbo, MD³, Craig C Hofmeister, MD, MPH⁴, Michael Freitas¹^*, Don M Benson, MD, PhD⁴ and Flavia Pichiorri, PhD⁵

¹The Ohio State University, Columbus
²A.O.U. San Giovanni Battista, Manchester, England
³Department of Hematology, University of Torino, Torino, Italy
⁴Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH
⁵Internal medicine, The Ohio State University, Columbus, OH

1815

Netrin-1 and Its Receptors Unc5b and DCC May be Useful Targets for Preventing Multiple Myeloma Bone Lesions

Aránzazu Mediero¹^*, Amitabha Mazumder, M.D.² and Bruce Cronstein¹^*

¹NYU School of Medicine, New York, NY
²NYU School of Medicine, NYU Cancer Center, New York, NY

1816

In Vitro and In Vivo Efficacy of a Novel Orally Bioavailable Beta-Catenin Inhibitor-BC2059- As Monotherapy or in Combination with Proteasome Inhibitors in Multiple Myeloma

Ioanna Savvidou, MD, PhD student¹^*, Tiffany T. Khong, PhD¹, Stephen K. Horrigan, PhD²^* and Andrew Spencer¹

¹Myeloma Research Group, Alfred Hospital-Monash University, Melbourne, Australia
²BetaCat Pharmaceuticals, Gaithersburg, MD

1817

Peripheral B Cells from Patients with MGUS and Multiple Myeloma (MM) Can Be Stimulated by Paraprotein-Target Specific T-Helper Cells to Produce Paraprotein-Identical Monoclonal Antibodies: Rationale for PARs, a Novel Therapeutic Approach with Ultimate Specificity in MGUS/MM

Frank Neumann, PhD^*, Boris Kubuschok, MD, Klaus-Dieter Preuss, PhD^*, Claudia Schormann^* and Michael Pfreundschuh, MD

José Carreras Center for Immuno- and Gene Therapy and Internal Medicine I, Saarland University Medical School, Homburg, Germany

1818

Next Generation XPO1 Inhibitor KPT-8602 for the Treatment of Drug-Resistant Multiple Myeloma

Joel G Turner, PhD¹, Jana L Dawson, BS²^*, Christopher L Cubitt, PhD³^*, Erkan Baluglo, PhD⁴^*, Steven Grant, MD⁵, Yun Dai, PhD⁶, Kenneth H Shain, MD, PhD³, William S. Dalton, PhD, MD⁷, Sharon Shacham⁸^*, William Senapedis, PhD⁸^* and Daniel M Sullivan, MD⁹

¹Bone Marrow Transplant Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
²Bone Marrow Transplant Program, Moffitt Cancer Center, Tampa, FL
³Moffitt Cancer Center, Tampa, FL
⁴Karyopharm Therpeutics, Newton, MA
⁵Massey Cancer Center, Virginia Commonwealth University, Richmond, VA
⁶Virginia Commonwealth University, Richmond, VA
⁷H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
⁸Karyopharm Therapeutics, Inc, Newton, MA
⁹Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

1819

Targeting Redox Overcomes Proteasome Inhibitor Resistance in Multiple Myeloma

Nathan G. Dolloff, PhD, Leticia Reyes^*, Brittany Smith^*, John Fairbanks Langenheim, PhD^* and Yefim Manevich^*

Medical University of South Carolina, Charleston, SC

1820

Stem Cell-like Characteristics of MM Plasma Cells Vary By ROS Levels: Implications for Targeted Therapy

Priyangi A Malaviarachchi, BS^*, Donald E Turner, BS^*, Caleb K. Stein, MS^*, Bart Barlogie, MD, PhD, Gareth J Morgan, MD PhD, Joshua Epstein, DSc, Shmuel Yaccoby, PhD and Sarah K. Johnson, PhD

Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR

1821

Oral Proteasome Inhibitor Marizomib and IMiD® Imunomodulatory Drug Pomalidomide Trigger Synergistic Anti-Myeloma Activity and Enhanced Proteasome Inhibition in Vitro and In Vivo

Deepika Sharma Das, PhD¹^*, Arghya Ray, PhD¹, Yan Song, Ph.D¹^*, Paul Richardson, MD¹, Mohit Trikha, PhD²^*, Dharminder Chauhan, PhD¹ and Kenneth C Anderson, MD³

¹The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
²Triphase Accelerator, San Diego, CA
³LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

1822

Mimicking the Myeloma Niche: A 3D Bone-Derived Co-Culture System to Selectively Assess Bystander BMSCs and to Perform High-Throughput Drug Screening in Multiple Myeloma

Johannes M. Waldschmidt, MD¹^*, Dagmar Wider¹^*, Andreas R. Thomsen, MD²^*, Claudius Klein³^*, Christine Aldrian²^*, Martin Kortuem, MD⁴^*, Marie Follo, PhD³^*, Julia Schüler, DVM, PhD⁵^*, Justus Duyster, MD, PhD⁶^*, Monika Engelhardt, MD, PhD³ and Ralph Wäsch, MD, PhD¹^*

¹Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany
²Department of Radiation Oncology, University of Freiburg Medical Center, Freiburg im Breisgau, Germany
³Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg im Breisgau, Germany
⁴Division of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ
⁵Department Head In Vivo Tumorbiology, Oncotest GmbH, Freiburg, Germany
⁶Dept. of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Freiburg, Germany

1823

Maternal Embryonic Leucine Zipper Kinase (MELK): a Novel Marker of Poor Prognosis and Attractive Drug Target in High-Risk Patients with Multiple Myeloma

Arnold Bolomsky¹^*, Karin Schlangen²^*, Artur Köhler³^*, Goran Mitulovic³^*, Wolfgang Schreiner²^*, Niklas Zojer, MD¹^* and Heinz Ludwig¹

¹Department of Medicine I, Wilhelminenhospital, Wilhelminen Cancer Research Institute, Vienna, Austria
²Center for Medical Statistics, Informatics and Intelligent Systems, Section for Biosimulation and Bioinformatics, Medical University of Vienna, Vienna, Austria
³Klinisches Institut für Labormedizin, Proteomics Core Facility, Medical University of Vienna, Vienna, Austria

1824

Ornithine Decarboxylase: Novel Prognostic Marker and Target for Multiple Myeloma Therapy

Sonali Panchabhai, MBBS¹^*, Ilana Miriam Schlam, MD², Sinto Sebastian Chirackal, PhD³^* and Rafael Fonseca, MD¹

¹Mayo Clinic, Scottsdale, AZ
²Collaborative Research Building, Scottsdale, AZ
³Haematology and Oncology, Mayo Clinic, Scottsale, AZ

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^*signifies non-member of ASH

652.P1.56 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster I