57th ASH Annual Meeting and Exposition (December 5-8, 2015): 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Acute Myeloid Leukemia: Exploiting New Therapeutic Targets and Novel Technologies

Molecular Pharmacology and Drug Resistance in Myeloid Diseases Oral and Poster Abstracts
Oral

W307, Level 3 (Orange County Convention Center)

Moderators:

Danilo Perrotti, MD, PhD, University of Maryland - Greenebaum Cancer Center and David B. Sykes, MD, PhD, Massachusetts General Hospital

Disclosures:

No relevant conflicts of interest to declare.

4:30 PM

787

New Allosteric Inhibitors of Mutant IDH1 in Acute Myeloid Leukemia

Ujunwa Cynthia Okoye-Okafor, MS¹, Boris Bartholdy, PhD²^*, Jessy Cartier²^*, Enoch Gao³^*, Beth Pietrak³^*, Alan R. Rendina³^*, Cynthia Rominger⁴^*, Chad Quinn³^*, Angela Smallwood³^*, Ken Wiggall⁵^*, Alexander Reif⁵^*, Stan Schmidt⁵^*, Hongwei Qi³^*, Huizhen Zhao³^*, Gerard Joberty³^*, Maria Faelth-Savitski³^*, Marcus Bantscheff³^*, Gerard Drewes³^*, Chaya Duraiswami³^*, Pat Brady³^*, Swathi-rao Narayanagari⁶^*, Ileana Antony-Debre, PhD, PharmD⁷^*, Kelly Mitchell⁶^*, Luis Carvajal⁸^*, Heng Rui Wang⁸^*, Laura Barreyro, PhD⁸, Yun-Ruei Kao⁸^*, Maximilian Christopeit, MD⁹, Elisabeth Paietta, PhD¹⁰, Hideki Makishima, MD, Ph.D.¹¹, Britta Will, PhD²^*, Nestor Concha³^*, Nicholas Adams¹²^*, Benjamin Schwartz³^*, Michael T. McCabe, PhD¹²^*, Jaroslaw P. Maciejewski, MD, PhD¹³, Amit Verma, MD¹⁴ and Ulrich Steidl, MD PhD⁸

¹MD/PhD student, Albert Einstein College of Medicine, Bronx, NY
²Albert Einstein College of Medicine, Bronx, NY
³Department of Molecular Discovery Research, GlaxoSmithKline, Collegeville, PA
⁴GlaxoSmithKline, Collegeville
⁵Cancer Epigenetics Discovery Performance Unit, GlaxoSmithKline, Collegeville, PA
⁶Albert Einstein College of Medicine, Bronx
⁷Albert Einstein College of Medicine, New York, NY
⁸Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY
⁹Oncology/Hematology, Internal Medicine, University Hospital Halle (Saale), Halle, Germany
¹⁰Cancer Center, The North Division of Montefiore Medical Center, Bronx, NY
¹¹Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH
¹²GlaxoSmithKline, Collegeville, PA
¹³Leukemia Program, Cleveland Clinic, Cleveland, OH
¹⁴Department of Medicine-Oncology, Albert Einstein College of Medicine, Bronx, NY

4:45 PM

788

MEN1112/OBT357, an Anti Bst1/CD157 Humanized Antibody Inducing Acute Myelogenous Leukemia (AML) Blast Depletion in an Autologous Ex Vivo Assay: A Potential New Targeted Therapy for AML

Adriano Venditti, MD¹, Francesco Buccisano², Luca Maurillo, MD³^*, Maria Ilaria Del Principe, MD¹^*, Andrea Coppola⁴^*, Patrizia Palomba⁵^*, Roberto Arriga⁴^*, Daniela Bellarosa⁶^*, Alessandro Bressan⁶^*, Keith Wilson⁷^*, Stefano Manzini⁸^*, Angela Capriati, MD, PhD⁹^*, Cecilia Simonelli, MD¹⁰^*, Monica Binaschi¹¹^*, Sergio Amadori, MD¹ and Giuseppe Sconocchia¹²^*

¹Hematology, University Tor Vergata, Rome, Italy
²Department of Hematology, University of Tor Vergata, Rome, Italy
³Hematology, Fondazione Policlinico Torvergata, Roma, Italy
⁴Department of Systems Medicine Prevention, University Tor Vergata, Rome, Italy
⁵Department of Biomedicine, University Tor Vergata, Rome, Italy
⁶Pharmacology Department, Menarini Ricerche, Pomezia (Rome), Italy
⁷Oxford Biotherapeutics, San Josè (CA)
⁸Preclinical Dev. Dept., Menarini Ricerche, Pomezia (Rome), Italy
⁹Menarini Ricerche S.p.A., Firenze, Italy
¹⁰Clinical Research, Menarini Ricerche S.p.A., Firenze, Italy
¹¹Menarini Ricerche SpA, Pomezia, Italy
¹²Institute of Translational Pharmacology, C.N.R, Rome, Italy

5:00 PM

789

Expression of Novel Immune Checkpoint Molecules PVR and PVRL2 Confers a Negative Prognosis to Patients with Acute Myeloid Leukemia and Their Blockade Augments T-Cell Mediated Lysis of AML Cells Alone or in Combination with the BiTE^® Antibody Construct AMG 330

Hauke Stamm, MSc¹^*, Felix Klingler, cand. med.¹^*, Daniela Pende, MD²^*, Eik Vettorazzi, MSc³^*, Michael Heuser, MD⁴, Ulrike Mock, PhD⁵^*, Carsten Bokemeyer, MD¹^*, Roman Kischel, MD⁶^*, Sabine Stienen, PhD⁶^*, Matthias Friedrich, PhD⁶^*, Michael Lutteropp, PhD⁶^*, Dirk Nagorsen, MD⁷, Jasmin Wellbrock, PhD¹^* and Walter Fiedler, MD¹

¹Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
²IRCCS AUO San Martino-IST, Genova, Italy
³Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
⁴Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
⁵Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
⁶Amgen Research (Munich) GmbH, Munich, Germany
⁷Global Clinical Development, Amgen, Thousand Oaks, CA

5:15 PM

790

FLT3 Inhibition and Retinoid Signaling Overcome Stromal Protection to Target FLT3/ITD-Expressing Leukemia Stem Cells in the Bone Marrow Microenvironment

Hayley S Ma, PhD¹^*, Megan E McCray, BA²^*, Courtney M Shirley, PhD¹^*, Amy S. Duffield, MD, PhD³, J Kyle Bruner¹^*, Li Li, PhD¹, Bao Nguyen, M.S.¹^*, Sarah Greenblatt, PhD¹^*, Eric Jung, BS⁴, Peter D. Aplan, MD⁵, Richard J Jones, MD², Donald Small, MD, PhD⁶ and Gabriel Ghiaur, MD, PhD²

¹Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
²Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
³Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
⁴Penn State Hershey College of Medicine, Hummelstown, PA
⁵NCI/CCR/Genetics branch, National Institutes of Health, Bethesda, MD
⁶Oncology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD

5:30 PM

791

Targeting the Hedgehog Signaling Pathway By PF-04449913 Limits the Self-Renewal of MDS-Derived Induced Potent Stem Cells (iPSC): Molecular Mechanisms

Tetsuzo Tauchi, M.D, Ph.D¹^*, Seiichi Okabe, MD, PhD¹^*, Seiichiro Katagiri, M.D.¹^*, Yuko Tanaka, M.D, Ph.D¹^*, Kaoru Tohyama, MD, PhD² and Kazuma Ohyashiki, MD, PhD¹

¹Department of Hematology, Tokyo Medical University, Tokyo, Japan
²Kawasaki Med. School, Kurashiki, Japan

5:45 PM

792

8-Chloro-Adenosine Inhibits Molecular Poor-Risk Acute Myeloid Leukemia (AML) and Leukemic Stem Cells (LSC) Growth Via Novel RNA- and ATP-Directed Mechanisms: A Novel Therapeutic Approach for AML

Ralf Buettner, PhD¹^*, Ching-Cheng Chen, PhD¹, Bijender Kumar, PhD¹^*, Lisa S Chen, Ph.D.²^*, Krister Wennerberg, PhD³^*, Ryan Thompson, MS⁴^*, Tea Pemovska, MSc³^*, Ling Li, PhD¹, Varsha Gandhi, Ph.D², Guido Marcucci, MD¹^*, Vinod Pullarkat, MD¹ and Steven T. Rosen, MD¹

¹Division of Hematopoietic Stem Cell and Leukemia Research of Beckman Research Institute, Gehr Family Center for Leukemia Research, City of Hope National Medical Center, Duarte, CA
²Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
³Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
⁴Chicago Medical School, Rosalind Franklin University, North Chicago, IL

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604.O2.6 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Acute Myeloid Leukemia: Exploiting New Therapeutic Targets and Novel Technologies