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604.P1.89 Molecular Pharmacology, Drug Resistance Poster I

Saturday, December 6, 2008: 5:30 PM-7:30 PM
Hall A (Moscone Center)
Targeting XIAP for Chemosensitization Purposes: Different Effect with Different Cytotoxic Drugs

Hugo Seca, BSc, MSc1*, Liliana Santos, BSc2*, Joana Figueiredo, BSc1*, Raquel T. Lima, BSc, MSc3*, Jose E. Guimaraes, MD, PhD4, Clara Sambade, MD, PhD5* and M. Helena Vasconcelos, BSc, MSc, PhD6*

1Cancer Biology Group, IPATIMUP, Porto, Portugal
2Cancer Biology Group, IPATIMUP and Faculty of Science of the University of Porto, Porto, Portugal
3Cancer Biology Group, IPATIMUP and Department of Microbiology, Faculty of Pharmacy of the University of Porto, Porto, Portugal
4Cancer Biology Group, IPATIMUP and Faculty of Medicine of the University of Porto and Hospital São João, Porto, Portugal
5Cancer Biology Group, IPATIMUP and Faculty of Medicine of the University of Porto, Porto, Portugal
6Cancer Biology Group, IPATIMUP and Department of Microbiology, Faculty of Pharmacy of the University of Porto and CEQUIMED, Porto, Portugal

CD200: a New Target for Immunotherapy in Hematologic Malignancies

Lorenzo Brunetti1*, Giovanna Abate1*, Marisa Gorrese1*, Maddalena Raia1*, Caterina Pascariello1*, Giulia Scalia1*, Bruno Rotoli2 and Luigi Del Vecchio1*

1Dipartimento di Biochimica e Biotecnologie Mediche and CEINGE, Università Federico II, Naples, Italy
2Divisione di Ematologia, Università Federico II, Naples, Italy

Anti Tumor Effect of 2-Oxoglutarate through Inhibition of Angiogenesis in a Murine Tumor Model

Ken Matsumoto*, Naoshi Obara*, Masaki Horie*, Ayano Naka*, Katsunori Utsugi* and Shigehiko Imagawa

Gschs, University of Tsukuba, Tsukuba, Japan

Targetting a Pro-Apoptotic Molecule BIM by Dexamethasone and MEK Inhibitors Synergistically Induces Apoptosis in Acute Lymphoblastic Leukemia Cells

Hisashi Harada, PhD, Anila A Rambal* and Zarah Liz G Panaguiton*

Virginia Commonwealth University, Richmond, VA

Pharicin B, a Novel Diterpenoid, Stabilizes Retinoic Acid Receptor-α Protein and Induces Differentiation of AML Cells in the Presence of Physiological Doses of ATRA

Guo-Qiang Chen1, Zhi-Min Gu2*, Mei-Yi Zhou1*, Ying-Li Wu1* and Ying Huang1*

1Department of Pathophysiology, Shanghai Jiaotong University School of Medicine, Shanghai, China
2Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

Adenanthin Upregulates c⁄ebp β Expression with Induction of Differentiation of the ATRA-Sensitive and -Resistant leukemic Cells

Ying-Li Wu*, Chuan-Xu Liu* and Guo-Qiang Chen

Department of Pathophysiology, Shanghai Jiaotong University School of Medicine, Shanghai, China

NPM-ALK Mutants in Kinase Domain Exhibit Altered Kinase Activity and Various Sensitivity to ALK Inhibitors

Lihui Lu1*, Arup Ghose2*, Matt Quail1*, Bruce Ruggeri1* and Mangeng Cheng1*

1Oncology Research, Cephalon Inc, West Chester, PA
2Chemistry, Cephalon Inc, West Chester, PA

Dose Escalated RAD001 (Everolimus) Enhances Chemosensitivity in Precursor-B Acute Lymphoblastic Leukemia, through a JNK Dependent Suppression of Cell Cycle Checkpoint Regulation

Philip O. Saunders, MB, MRCP, FRACP, FRCPA1*, Kenneth F. Bradstock, MB, PhD, FRACP, FRCPA2 and Linda J. Bendall, BSc, PhD1

1WICR, Westmead Millennium Institute, University of Sydney, Sydney, NSW 2145, Australia
2Department of Haematology, Westmead Hospital, Sydney, NSW 2145, Australia

A Novel Chromene-Based Pan-PI3 Kinase Inhibitor Displays Preclinical Activity in Leukemia and Myeloma

Xinliang Mao, MD, PhD1*, Tabitha W. Wood, PhD1*, Xiaoming Wang, PhD1*, Johnathan St-Germain, BSc2*, Michael F. Moran, PhD2*, Alessandro Datti, PhD3*, Jeff Wrana, PhD3*, Robert A. Batey, PhD4* and Aaron D. Schimmer, MD, PhD1

1Princess Margaret Hospital/ Ontario Cancer Institute, Toronto, ON, Canada
2The Hospital for Sick Children, Toronto, ON, Canada
3Mount Sinai Hospital, Toronto, ON, Canada
4Department of Chemistry, University of Toronto, Toronto, ON, Canada

The Para-Isomer of Nitric Oxide-Donating Acetylic Salicylic Acid (p-NO-ASA) Effectively Induces Cell Death in B-Cell Chronic Lymphocytic Leukemia (CLL) Cells at Low Micromolar Concentrations

Regina Razavi, M.Pharm.1*, Julian Paesler, M.Pharm.1*, Iris Gehrke, M.Sc.1*, Felix Erdfelder1*, Magdalena Hertweck1*, Alexandra Filipovich1*, Rajesh Kumar Gandhirajan, M.Sc.1*, Michael Hallek, MD2 and Karl Anton Kreuzer, M.D.1*

1Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University at Cologne, Cologne, Germany
2Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany

Identification of p53 Aberration-Dependent as Well as Non-p53-Mediated Resistance to MDM2 Inhibitors in Acute Myelogenous Leukemia

Jianting Long, MD1*, Peter Ouillette1*, Brian Parkin1*, Harry Erba2*, Shaomeng Wang2* and Sami Malek, MD2

1Internal Medicine Heme-Onco, University of Michigan, Ann Arbor, MI
2Comprehensive Cancer Ctr., Univ. of Michigan, Ann Arbor, MI

Cellular and Molecular Mechanisms of Sensitivity and Resistance of Hematopoietic Malignant Cells to Treatment with ch128.1Av, An Antibody-Avidin Fusion Protein Specific for Human Transferrin Receptor 1 (CD71)

Jose A Rodriguez1*, Gustavo Helguera, PhD1*, Tracy R Daniels, Ph.D.1*, David Casero Diaz-Cano, Ph.D.2*, Elizabeth Ortiz-Sanchez, PhD1*, Giovanni Coppola, Ph.D.3*, Matteo Pellegrini, Ph.D.2*, Otoniel Martinez-Maza, Ph.D.4* and Manuel L Penichet, M.D., Ph.D.1*

1Surgery, Surgical Oncology, University of California, Los Angeles, Los Angeles, CA
2Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA
3Neurogenetics, University of California, Los Angeles, Los Angeles, CA
4Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, CA

Effect of Second Mitochondria-Derived Activator of Caspases (Smac) Mimetic Compounds on Leukemic Cell Lines

Federica Servida, MS1*, Francesco Onida, MD2, Domenico Delia, MD3*, Cinzia Scavullo, MS1*, Daniele Lecis, MS3*, Pierfausto Seneci, DS4*, Carmelo Carlo Stella, MD3* and Giorgio Lambertenghi Deliliers, MD2

1Department of Pharmacology, Chemotherapy and Medical Tossicology - University of Milan, Fondazione Matarelli, Milan, Italy
2Department of Medical Science - O.U. Hematology 1 - CTMO, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena and University of Milan, Milan, Italy
3Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
4Centro Interdisciplinare di Studi Biomolecolari e Applicazioni Industriali, Milan, Italy

Analysis of Aurora B Kinase in Non-Hodgkin’s Lymphoma

Takayuki Ikezoe1, Tamotsu Takeuchi2*, Chie Nishioka1*, Yoshihiro Adachi2*, Mutsuo Furihata2*, H. Phillip Koeffler, MD3 and Akihito Yokoyama1*

1Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan
2Tumor Pathology, Kochi University, Nankoku, Japan
3Cedars-Sinai Medical Center, Los Angeles, CA

Hedgehog Inhibitors Reduce the Survival and Drug Resistance in CD34+ Leukemic Cells

Masayoshi Kobune, MD, PhD, Kazuyuki Murase, MD, PhD*, Satoshi Iyama, MD, PhD*, Tsutomu Sato, MD, PhD*, Yutaka Kawano, MD, PhD*, Shohei Kikuchi, MD, PhD*, Koji Miyanishi, MD, PhD*, Rishu Takimoto, MD, PhD* and Junji Kato, MD, PhD*

Fourth Dept. of Internal Med., Sapporo Medical University, Sapporo, Japan

Blockade of mTOR Signaling Potentiates the Ability of Histone Deacetylase Inhibitor to Induce Growth Arrest and Differentiation of Acute Myelogenous Leukemia Cells

Chie Nishioka1*, Takayuki Ikezoe1, Yang Jing1*, H. Phillip Koeffler, MD2 and Akihito Yokoyama1*

1Hematology and Respiratory Medicine, Kochi University, Nankoku, Japan
2Cedars-Sinai Medical Center, Los Angeles, CA

Outcome of Aurora Kinase Inhibition of Acute Myeloid Leukemia by AT9283 Is Dependent upon the Presence or Absence of Mutations in Type 1 Oncogenic Kinase Signalling Pathways

John Goodall1*, Matthew S Squires2*, Vicky Lock3*, Farhad Ravandi, MBBS4, Hagop M Kantarjian5, James Foran, MD6, Neil T Thompson7* and John F Lyons2*

1Biology, Astex Therapeutics, Cambridge, United Kingdom
2Astex Therapeutics Ltd., Cambrigde, United Kingdom
3Translational Biology, Astex Therapeutics, Cambridge, United Kingdom
4Department of Leukemia, M.D. Anderson Cancer Center, Houston, TX
5The University of Texas M. D. Anderson Cancer Center, Houston, TX
6University of Alabama at Birmingham, Birmingham, AL
7Astex Therapeutics, Cambridge, United Kingdom

Therapeutic Nucleic Acids: A Potential Source of Resistance to Cancer, Antiviral and Immunosuppressive Therapy

Raymund Buhmann1*, Ting Yang2*, Monica Schifferer3*, Martin Obermeier4*, Gundula Jaeger4* and Hans-Jochem Kolb5

1Medical Clinic III, Klinikum Großhadern Medical Center (KGMC), Klinikum Großhadern, Ludwig-Maximilians-University Munich, Munich, Germany
2Department of Hematology, Union Hospital, Fujian Medical University, Fuzhou, Fujian, China
3HelmholtzZentrum münchen, Munich, Germany
4Virologie, Max von Pettenkofer-Institut, Munich, Germany
5Medical Clinic III, Klinikum Großhadern Medical Center (KGMC), Klinikum Großhadern, Ludwig-Maximilians-University Munich, Munich, Germany

Detection of Twelve Nucleotides Instertion in the BCR-ABL Kinase Domain in an Imatinib-Resistant but Dasatinib-Sensitive Patient with Bi-Phenotypic Acute Leukemia

Sandrine Hayette, PhD1*, Kaddour Chabane, BSc2*, Andrei Tchirkov, MD, PhD3*, Marc G Berger, MD, PhD4, jean-Pierre Magaud, MD, PhD5*, Franck E Nicolini, MD, PhD6 and Olivier Tournilhac, MD, PhD7*

1Hematology (Biology) and UMR5239 CNRS, Hospices civils de Lyon Centre Hospitalier Lyon Sud, Pierre Bénite, France
2Hematology (biology), Centre Hospitalier Lyon Sud, Pierre Benite, France
3Service de Cytogénétique Médicale, CHU de Clermont-Ferrand and EA3846, Clermont-Ferrand, France
4Hematology (Biology), CHU, Clermont-Ferrand, France
5Hematology (Biology) and UMR5239 CNRS, Hospices civils de Lyon Centre Hospitalier Lyon Sud, Pierre Benite, France
6Hematology Department, Hospital E. Herriot, Lyon, France
7Hematology, CHU Clermont Ferrand, Clermont Ferrand, France

Identification of Heat Shock Protein 32 (Hsp32) as a Novel Target in Acute Lymphoblastic Leukemia (ALL)

Renata A. Meyer, MD1*, Harald Herrmann, MD1*, Karoline V. Gleixner, MD1*, Alexander Gruze2*, Sabine Cerny-Reiterer, MD1*, Rainer Hubmann, PhD1*, Medhat Shehata, MD1*, Matthias Mayerhofer, MD3*, Wolfgang R. Sperr, MD1*, Winfried F. Pickl, MD2*, Junia V. Melo, PhD4*, Gahininath Y. Bharate5*, Ulrich Jäger, MD1*, Hiroshi Maeda, MD, PhD5* and Peter Valent, MD1

1Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
2Institute of Immunology, Medical University of Vienna, Vienna, Austria
3Clinical Institute of Medical & Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
4Haematology Division, IMVS, University of Adelaide, Adelaide, Australia
5Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan

Targeting the Mnk Pathway Enhances Chemotherapy-Induced Antileukemic Responses

Jessica K Altman, Heather Glaser*, Amanda Redig*, Antonella Sassano*, Martin S Tallman and Leonidas C Platanias

Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL

Identification of Core Gene Signature Associated with Synergism Between ABT-869, a FLT3 Inhibitor and SAHA, a HDAC Inhibitor in AML with FLT3-ITD Mutation

Jianbiao Zhou, MD, MS1, Chonglei Bi, Bsc1*, Shaw-Cheng Liu1*, Wee-Joo Chng, MD1*, Kian-Ghee Tay, Bsc1*, Hanry Yu, Ph.D.2*, Keith Glaser, Ph.D.3*, Daniel Albert, PhD, BSc4*, Steven K Davidsen, Ph.D.4* and Chien-Shing Chen, MD, PhD5

1Dept. of Medicine, Yong Loo Lin School of Medicine, National Univ. of Singapore, Singapore, Singapore
2Department of Physiology, National University of Singapore, Singapore, Singapore
3Cancer Research, Abbott Laboratories, Abbott Park, IL
4Abbott Laboratories, Abbott Park, IL
5Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Treatment with Hsp90 Inhibitor, 17-AAG Overcomes Resistance to Small Molecule FLT3-Inhibitors in FLT3/ITD-Positive Leukemia Cells Harboring N676K-Mutation

Yosuke Minami, MD, PhD1, Yuka Nomura1*, Akihiro Abe, MD, PhD1, Ryohei Tanizaki, MS1*, Yachiyo Kuwatsuka1*, Hitoshi Kiyoi, MD, PhD2* and Tomoki Naoe, MD3

1Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
2Department of Infectious Disease, Nagoya University Hospital, Nagoya, Japan
3Japan Adult Leukemia Study Group, Japan

DNA Repair Gene, XRCC1 Polymorphisms Are Associated with Chemotherapy Induced Toxicity in Patients with Diffuse Large B Cell Lymphoma Who Received Frontline R-CHOP Chemotherapy

In-Suk Kim1, Gyeong-Won Lee2*, Hoon-Gu Kim2*, Sun-Young Kong, MD, PhD3 and HyeonSeok Eom, MD, PhD4

1Laboratory Medicine, Gyeongsang national university hospital, Jinju, South Korea
2Internal Medicine, Gyeongsang national university hospital, Jinju, South Korea
3Hematologic Malignancies Branch, National Cancer Center, Goyang-si, Gyeonggi-do, South Korea
4National Cancer Ctr., Goyang-Si

The CXCR4 Antagonist AMD3100 Impairs Survival of AML Cells and Induces Their Differentiation

Sigal Tavor, MD1*, Manny Eisenbach1*, Jasmine Jacob-Hirsch2*, Tammar Golan, PhD1*, Isabelle Petit, PhD1*, Katz Ben-Zion, PhD1*, Sigi Kay, PhD1*, Shoshana Baron1*, Ninette Amariglio, PhD2, Varda Deutsch, PhD1, Elizabeth Naparstek, MD1* and Gideon Rechavi, MD, PhD2*

1Institute of hematology and bone marrow transplantation, Sourasky Medical Center, Tel Aviv, Israel
2Cancer Research Center, Sheba M.C., Tel-Hashomer, Israel

Identification of Genes Associated with Resistance and Response in Vivo to Therapy with Rituximab, Fludarabine and Cyclophosphamide in Patients with Chronic Lymphocytic Leukemia

Medhat Shehata, MD1*, Dita Demirtas, MD1*, Stefanie Tauber, MD2*, Susanne Schnabl1*, Martin Bilban, PhD2*, Martin Hilgarth1*, Oswald Wagner, MD2*, Christa Fonatsch, MD3*, Ilse Schwarzinger, MD2*, Georg Hopfinger, MD4*, Karin Eigenberger, MD1*, Cathrin Skrabs, MD1*, Daniel Heintel, MD5*, Edit Anna Porpaczy, MD1*, Katrina Vanura, PhD1*, Stephan Stilgenbauer, MD, PhD6, Michael Hallek, MD7, Josef D. Schwarzmeier, MD1, Rainer Hubmann, PhD1*, Alexander Gaiger, MD1* and Ulrich Jaeger, MD1

1Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria
2Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria
3Medical Genetics, Medical University of Vienna, Vienna, Austria
4Department of Medicine III, Hanusch Hospital, Vienna, Austria
51st Department of Internal Medicine, Center for Oncology and Hematology, Wilhelminenhospital
6Internal Medicine III, University of Ulm, Ulm, Germany
7Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany

COX-2 Inhibition Suppresses the Interferon-γ-Induced Expression of Indoleamine 2,3-Dioxygenase (IDO) in Human Leukemia Cell Lines

Maria Grazia Iachininoto, BSc1*, Eugenia Rosa Nuzzolo, BSc1*, Anna Di Maggio, BSc2*, Giuseppina Bonanno, BSc3*, Andrea Mariotti, BSc3*, Annabella Procoli, BSc3*, Maria Corallo, BSc3*, Giuseppe Leone, MD1*, Raimondo De Cristofaro, MD2* and Sergio Rutella, MD, PhD1

1Hematology, Catholic University Medical School, Rome, Italy
2Medicine, Catholic University Medical School, Rome, Italy
3Gynecology, Catholic University Medical School, Rome, Italy

Bcr-Abl-Independent Activation of Src Kinases Associated with Development of Dasatinib Resistance in a CML Patient

Jitka Veselovska, MSc1*, Renata Solna, PhD1*, Marie Jarosova, PhD2*, Edgar Faber, MD, PhD2*, Helena Urbankova, MSc2*, Milena Holzerova, MSc2*, Jana Balcarkova, MSc2*, Karel Indrak, MD, PhD2* and Vladimir Divoky, PhD1

1Dept. of Biology, Palacky Univ. Faculty of Med., Olomouc, Czech Republic
2Department of Hemato-Oncology, University Hospital Olomouc, Olomouc, Czech Republic

A Novel Heat Shock Protein (HSP) 90 Inhibitor KW-2478 shows Activity in B-Cell Malignancies in Vitro and in Vivo

Simone Juliger1*, Takayuki Nakashima2*, Lenushka Maharaj1*, Toshihiko Ishii2*, Hiroshi Nakagawa2*, Yutaka Kanda2*, Heather Oakervee1*, James Cavenagh1, Shiro Akinaga2*, Yukimasa Shiotsu2* and Simon P Joel1*

1St. Bartholomew's Hospital, London, United Kingdom
2Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan

Pharmacokinetics and Pharmacodynamics of High Dose Methotrexate in Children with Acute Lymphoblastic Leukemia and down Syndrome: a Case Cohort StudyClinically Relevant Abstract

T. Buitenkamp, MSc1*, R. Mathot, Dr.2*, A. Vulto, Prof.dr.2*, A. Veerman, MD, PhD3*, E. van Wering4, R. Pieters, MD, PhD1, M. Van Den Heuvel, MD, PhD1 and Christian M Zwaan, MD, PhD1

1Dept. of Pediatric Hem./Onc, Erasmus MC, Rotterdam, Netherlands
2Department of Pharmacy, Erasmus MC, Rotterdam, Netherlands
3Ped. Oncology, VUmc, Amsterdam, Netherlands
4Dutch Childhood Oncology Group (DCOG), The Hague, Netherlands

The Effect of ABC Transporters and FLT3 Status on the Activity of the Aurora Kinase B Inhibitor AZD1152 in AML Cells

Martin Grundy, BSc1*, Shili Shang, MD, MSc1*, C. Seedhouse, PhD2*, Nigel H. Russell, MD3 and Monica Pallis, PhD4*

1Academic Haematology, UNIVERSITY OF NOTTINGHAM, Nottingham, United Kingdom
2Academic Haematology, Nottingham University Hospital, Nottingham, United Kingdom
3Centre for Clinical Haematology, Nottingham University Hospital, Nottingham, ARRAY(0xc1c3fa4)
4Academic Haematology, Nottingham University Hospitals, Nottingham, United Kingdom

Berberine Induces Apoptosis in Acute Lymphoblastic Leukemia Cells through Downregulation of the MDM2 Oncoprotein

Xiaoling Zhang*, Lubing Gu, MD, Noopur Shah* and Muxiang Zhou, MD

Pediatrics, Emory University, Atlanta, GA

A Macromolecular Signaling Complex Formed by CXCR4, VLA4 and hERG1 K+ Channels Mediates Bone Marrow-Induced Chemo-Resistance in Childhood Acute Lymphoblastic Leukemias: Shortcoming Effects of hERG1 Channels Inhibitors

Serena Pillozzi1*, Marika Masselli2*, Amedeo Amedei3*, Giuseppe Gaipa4*, Andrea Biondi4*, Dario Campana, MD, PhD5, Andrea Becchetti6* and Annarosa Arcangeli, MD, PhD7

1Exp. Pathology and Oncology, University of Florence, Florence, Italy
2Experimental Pathology and Oncology, University of Florence, Florence, Italy
3Department of Internal Medicine, University of Florence, Florence, Italy
4Pediatric Department, Laboratory of Cell Therapy, San Gerardo Hospital, Monza, University of Milano-Bicocca, Monza, Italy
5Oncology and Pathology, St. Jude Children's Research Hospital, Memphis, TN
6Biotechnology and Biosciences, University of Milano, Milano, Italy
7Exp. Pathology and Oncology, University of Florence, Firenze, Italy

Microenvironmental Factors Determine the Sensitivity of Acute Myeloid Leukemia Cells to Tyrosine Kinase Inhibitors

Akira Shimada, MD, PhD1, Shelley Orwick1*, Hiroyuki Fujisaki, MD., PhD2, Dario Campana, MD., PhD2 and Sharyn D. Baker, PharmD., PhD1*

1Pharmaceutical Science, St. Jude Children's Rsrch Hosp., Memphis, TN
2Oncology, St. Jude Children's Rsrch Hosp., Memphis, TN

Targeting Anaplerotic Pathways That Support Fatty Acid Metabolism as a Therapeutic Strategy for Hematological Malignancies: The Achilles’ Heel of the Warburg Effect

Ismael J. Samudio, PhD1*, Michael Fiegl, PhD1*, Marina Konopleva, MD, PhD2, Kumar Kaluarachchi, PhD3*, John S. McMurray, PhD, BS3*, Borys Korchin1*, Karen Clise Dwyer, PhD1*, Romain Harmancey, PhD4*, Patrick Guthrie, BS4*, Heinrich Taegtmeyer, MD, PhD4* and Michael Andreeff, MD, PhD1

1Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
2Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX
3Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX
4Division of Cardiology, University of Texas Medical School, Houston, TX

Novel Small Molecule Pim Protein Kinase Inhibitors Induce Cell Cycle Arrest and Apoptosis in Human Leukemias: A Potential Therapeutic Approach

Yingwei Lin, MD., PhD.1, Jin H. Song, PhD.2*, Zhenhua Zhang3*, Peter D. Aplan, MD3, Charles D Smith, PhD4*, Andrew Kraft, MD5 and Zanna M Beharry, PhD.6*

1Pediatrics, Medical University of South Carolina, Charleston, SC
2Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC
3Genetics Branch, NIH, NCI, CCR, Bethesda, MD
4Department of Pharmaceutical and Biomedical Sciences, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC
5Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC
6Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC

The Combination of a Histone Deacetylase (HDAC) Inhibitor with the BCL-2 Inhibitor GX15-070 Has Synergistic Antileukemia Effect by Inducing Both Apoptotic and Autophagic Pathways

Yue Wei, PhD1*, Tapan Kadia, MD1, Weigang Tong, MD, PhD1*, Susan O'Brien, MD1, Jean Viallet, MD2 and Guillermo Garcia-Manero, MD1

1Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX
2GeminX, Malvern, PA

Bortezomib Overcomes Cell Adhesion-Mediated Drug Resistance Via Down-Regulation of VLA-4 Expression in Multiple Myeloma

Kaoru Hatano1*, Jiro Kikuchi2*, Masaaki Takatoku1*, Rumi Shimizu2*, Taeko Wada2*, Masuzu Ueda1*, Masaharu Nobuyoshi1*, Iekuni Oh1*, Kazuya Sato1*, Takahiro Suzuki1*, Katsutoshi Ozaki1*, Masaki Mori1*, Tadashi Nagai1*, Kazuo Muroi1*, Yasuhiko Kano3*, Yusuke Furukawa2* and Keiya Ozawa1

1Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsukeshi, Japan
2Division of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Shimotsukeshi, Japan
3Division of Hematology, Tochigi Cancer Center, Utsunomiyashi, Japan

Bortezomib-Induced Apoptosis in Cutaneous T-Cell Lymphoma and Adult T-Cell Leukemia/Lymphoma Cells Partially Depends on up-Regulation of Noxa, Functional Repression of Mcl-1, and Down-Regulation of C-Flip and XIAP

Masaki Ri1*, Shinsuke Iida1*, Takashi Ishida1*, Asahi Ito1*, Hiroki Yano1*, Atsushi Inagaki1*, Jianmin Ding1*, Fumiko Mori1*, Shigeru Kusumoto1*, Hirokazu Komatsu1*, Atae Utsunomiya2* and Ryuzo Ueda1

1Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
2Dept. of Hematology, Imamura Bun-in Hospital, Kagoshima, Japan

Obesity Alters the Pharmacokinetics of Vincristine in MiceClinically Relevant Abstract

James W Behan1*, Vassilios I Avramis, PhD2*, Jason P Yun1*, Anna Butturini, MD2 and Steven D Mittelman, MD, PhD1*

1Division of Endocrinology, Childrens Hospital Los Angeles, Los Angeles, CA
2Hematology/Oncology, Childrens Hospital Los Angeles, Los Angeles, CA

HERG K+ Channel Is Essential for Leukemic Cell Migration Induced by SDF-1

Huiyu Li1*, Yi-Mei Du2*, Linlin Guo1*, Tiannan Guo1*, Shenghua Jie1*, Wen Du1*, Xiangjun Chen1*, Wei Liu1*, Jiahua Zhang1*, Linlin Fan1*, Anruo Zou2*, Songyu Zhang2* and Shiang Huang1

1Center for Stem Cell Research and Application, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China
2Ion Channelopathy Research Center, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China

Panobinostat (LBH589) a Promising New Partner for Combination with Doxorubicin in Acute  Myeloid Leukemia

Patricia Maiso1*, Enrique Colado1*, Enrique M Ocio1*, Mercedes Garayoa1*, Peter Atadja2*, Atanasio Pandiella1* and J.F. San Miguel, MD, PhD1

1Centro de Investigación del Cáncer IBMCC/CSIC, University of Salamanca, Salamanca, Spain
2Novartis Pharmaceuticals, NJ

GF-15, a Novel Inhibitor of Centrosomal Clustering, Suppresses Tumor Growth in Vivo

Marc S Raab1, Iris Breitkreutz1, Blanca Rebacz2*, Thu Nguyen3*, Patrick J. Hayden1*, Mads H Clausen4*, Thomas O. Larsen4*, Johannes Fruehauf3*, Kenneth C. Anderson1* and Alwin Kraemer2*

1Dana-Farber Cancer Inst., Boston, MA
2CCU Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany
3Gastroenterology, Beth Israel Medical Center
4BioCentrum, University of Denmark

KW-2449, a Novel Multi-Kinase Inhibitor, Suppresses the Growth of Imatinib-Resistant Ph+ Leukemia Including BCR-ABL/T315I Both in Vitro and in Vivo

Yukimasa Shiotsu, PhD1, Hitoshi Kiyoi, MD, PhD2, Ryohei Tanizaki, MD, PhD3*, Yosuke Minami, MD, PhD4, Akihiro Abe, MD, PhD3, Yuichi Ishikawa, MD, PhD2*, Kenichi Ishii1*, Makiko Shimizu1*, Yutaka Kanda, PhD1*, Yuko Sato, MD, PhD5, Shiro Akinaga, PhD6*, Jorge Cortes, MD7 and Tomoki Naoe, MD, PhD3*

1Oncology Group, Fuji Research Park. Kyowa Hakko Kirin Co Ltd, Shizuoka, Japan
2Department of Infectious Disease, Nagoya University School of Medicine, Nagoya, Japan
3Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
4Devision of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
5Dept. of Pathology, Rsrch. Inst. International Med., Tokyo, Japan
6Kyowa Hakko Kirin Co Ltd, Tokyo, Japan
7M.D. Anderson Cancer Center, Houston, TX

*signifies non-member of ASH