50th ASH Annual Meeting and Exposition (December 6 - 9, 2008): Chronic Myeloid Leukemia - Biology and Pathophysiology Excluding Therapy Poster I

Saturday, December 6, 2008: 5:30 PM-7:30 PM

Hall A (Moscone Center)

Targeting Autophagy Potentiates Imatinib-Induced Cell Death in Philadelphia Positive Cells Including Primary CML Stem Cells

Cristian Bellodi¹^*, Maria Rosa Lidonnici²^*, Ashley Hamilton³^*, Gudmundur V Helgason³^*, Angela R Soliera²^*, Mattia Ronchetti²^*, Sara Galavotti¹^*, Kenneth W Young¹^*, Tommaso Selmi¹^*, Richard A. Van Etten⁴^*, Nicholas Donato⁵, Ann Hunter⁶^*, David Dinsdale¹^*, Elena Tirro'⁷^*, Paolo Vigneri⁸^*, Pierluigi Nicotera¹^*, Martin J.S. Dyer¹, Tessa Holyoake³, Bruno Calabretta²^* and Paolo Salomoni¹^*

¹MRC Toxicology Unit, Leicester, United Kingdom
²Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA
³Paul O'Gorman Leukaemia Research Centre, University of Glasgow, Gartnavel General Hospital, Glasgow, United Kingdom
⁴Tufts Medical Center, West Roxbury, MA
⁵Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI
⁶Department of Pathology, Royal Infirmary Hospital, Leicester, United Kingdom
⁷Department of Biomedical Sciences, University of Catania, Catania, Italy
⁸Department of Biomedical Sciences, University of Catania Medical School, General Pathology Section, Catania, Italy

1071

Preferentially Expressed Antigen in Melanoma (PRAME) Expression in Normal and CML CD34+ Progenitor Cells Impairs Myeloid Differentiation

Vivian Oehler¹, Carrie Cummings¹^*, Kathleen Sabo²^*, Brent Wood³, Katherine Guthrie¹^*, Ted Gooley¹^*, Era Pogosova-Agadjanyan¹^*, Paula Ladne¹^*, Derek Stirewalt¹^*, Janis L. Abkowitz² and Jerald Radich¹^*

¹Clinical Research Division, Fred Hutchinson Cancer Research Ctr., Seattle, WA
²Division of Hematology, University of Washington, Seattle, WA
³Seattle Cancer Care Alliance, Seattle, WA

1072

Growth of p210Bcr-Abl Transformed Human Hematopoietic Stem Cells in Immunodeficient Mice

Hardik V Modi, MSc¹^*, Leonard Shultz, PhD²^* and Ravi Bhatia, MD³

¹Stem cell and Leukemia Research, City Of Hope, Duarte, CA
²The Jackson Laboratory, Bar Harbor, ME
³City of Hope National Medical Center, Duarte, CA

1073

N-Cadherin-Mediated Microenvironmental Interactions Protect CML Stem Cells from Imatinib Mediated Apoptosis

Bin Zhang, MD, PhD¹^*, Tinisha McDonald¹^*, Tessa Holyoake, PhD.²^*, Dario Campana, MD., PhD³ and Ravi Bhatia, MD¹

¹Department of Hematopoietic Stem cell and Leukemia Research, City of Hope, Duarte, CA
²Div of Cancer Sciences & Molecular Pathology, University of Glasgow, Glasgow, United Kingdom
³Oncology, St. Jude Children's Research Hosp., Memphis, TN

1074

Deregulated Bcl-2 Family Expression Drives Chronic Myeloid Leukemia Cancer Stem Cell Survival

Daniel Jacob Goff¹^*, Annelie Abrahamsson²^*, Ifat Geron²^* and Catriona Jamieson, MD, PhD³

¹Biomedical Sciences, University of California San Diego, La Jolla, CA
²University of California San Diego, La Jolla, CA
³Department of Medicine, University of California San Diego, La Jolla, CA

1075

Comparative Effects of Wild Type and T315I Mutated bcr-ABL in Murine Embryonic Stem-Cell Derived Hematopoiesis

Michael Melkus, PhD¹^*, Maria Theresa Mitjavila-Garcia, PhD²^*, Marie-Laure Bonnet³^*, Nathalie Sorel⁴^*, Jean-Claude Chomel⁴^*, Annelise Bennaceur-Griscelli, MD, PhD⁵^* and Ali G Turhan, M.D., PhD³

¹Inserm 602 and I-Stem, Evry, France
²Human ES Cell Core facility, Inserm 602, Villejuif, France
³Division of Laboratory Hematology and Oncology, Poitiers University Hospital, EA 3805, Poitiers, France
⁴Division of laboratory Hematology and Oncology, Poitiers University Hospital, EA 3805, Poitiers, France
⁵Human Es cell core facility, Inserm 602, Villejuif, France

1076

Evaluation of the Role of STAT3 in the Self-Renewal of Primitive Chronic Myelogenous Leukemia (CML) Stem Cells

Severine Martin-Lannerée, PhD¹^*, Marie-Laure Bonnet²^*, Caroline Mayeur-Rousse, MD²^*, Angelina Bertrand²^*, Marie-Claude Meunier²^*, Lydia Roy, MD³^*, Francois Guilhot, MD⁴, Isabelle Dusanter-Fourt, PhD⁵^* and Ali G Turhan, M.D., PhD²

¹CNRS (UMR8104) - Inserm, U567, Institut Cochin, Universite Paris Descartes, Paris, France
²Division of Laboratory Hematology and Oncology, Poitiers University Hospital, EA 3805, Poitiers, France
³Onco-Hematology and Cell Therapy, CIC-Inserm 802, Poitiers, France
⁴Onco-Hematology and Cell Therapy, CIC-Inserm 802, Hopital Jean Bernard, Poitiers, France
⁵Institut Cochin,Université Paris Descartes, Paris, France

1077

Mtss1 Suppresses BCR-ABL Induced Cell Migration and Is Downregulated in CML Stem Cells

Mirle Schemionek¹^*, Shuchi Agrawal, PhD¹^*, Martin Stehling, PhD²^*, Daniel G. Tenen, MD³, Ashley Hamilton⁴^*, Tessa Holyoake, MD, PhD⁴, Ulrich Steidl, MD, PhD⁵, Wolfgang E. Berdel, MD¹^*, Albrecht Schwab, MD⁶^*, Carsten Müller-Tidow, MD¹^* and Steffen Koschmieder, MD¹

¹Dept. of Medicine (Hematology and Oncology), University of Münster, Münster, Germany
²Max-Planck Institute for Molecular Biomedicine, Münster, Germany
³Harvard Inst. of Med., Boston, MA
⁴Paul O'Gorman Leukaemia Research Centre, University of Glasgow, Gartnavel General Hospital, Glasgow, United Kingdom
⁵Department of Cell Biology and Albert Einstein Cancer Center, Albert Einstein College of Medicine, New York, NY
⁶Dept. of Physiology II, University of Münster, Münster, Germany

1078

A Novel Strategy for Expanding Primitive Leukemic Cells from Chronic Phase CML Patients by Forced Overexpression of a NUP98-HOXA10 Homeodomain Fusion Gene

Ivan Sloma, PhD^*, Suzan Imren, MD^*, Yun Zhao, PhD^*, Keith Humphries, MD, PhD^* and Connie J. Eaves, PhD

Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, BC, Canada

1079

Low or Undetectable Numbers of Philadelphia Chromosome Positive (Ph+) Leukemia Cells in the Primitive (CD34^posCD38^neg) Stem Cell Fraction in Chronic Myeloid Leukemia (CML) Patients during Tyrosine Kinase Inhibitor Therapy

Satu Mustjoki, MD, PhD¹, Peter Rohon, MD²^*, Katrin Rapakko, MSc, PhD³^*, Sari Hernesniemi, MSc¹^*, Perttu Koskenvesa, MD¹^*, Tuija Lundán, MSc, PhD⁴^* and Kimmo Porkka, MD, PhD¹

¹Hematology Research Unit, Department of Medicine, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
²Hematology Research Unit, Helsinki University Central Hospital and University Hospital Olomouc, Helsinki, Finland
³Genetics Laboratory, Department of Laboratory, Oulu University Central Hospital, Oulu, Finland
⁴Hematology Research Unit, Department of Medicine and Laboratory of Molecular Pathology, HUSLAB, Helsinki University Central Hospital, Helsinki, Finland

1080

Beta-catenin Is Essential for Survival of Leukemia Stem Cells Insensitive to Kinase Inhibition in Mice with BCR-ABL Induced Chronic Myeloid Leukemia

Shaoguang Li¹, Yiguo Hu²^*, Yaoyu Chen³^* and Lori Douglas⁴^*

¹Department of Medicine, University of Massachusetts Medical School, Worcester, MA
²Department of Medicine, University of Massachusetts, Worcester, MA
³University of Massachusetts Medical School, Worcester, MA
⁴University of Massachusetts Medical School, Worcester

1081

A Novel β-catenin Inhibitor, AV65 Suppresses the Growth of CML Cell Lines Which Acquire Imatinib-Resistance Because of Abl Kinase Domain Mutations Including T315I and Hypoxia-Adaptation

Rina Nagao¹^*, Shinya Kimura, MD, PhD¹^*, Eishi Ashihara, MD, PhD², Miki Takeuchi, MD¹^*, Ruriko Tanaka, MMSc¹^*, Asumi Yokota, MMSc¹^*, Hisayuki Yao, MD¹^*, Jeffrey W Strovel³^*, Wieslaw M Cholody³^* and Taira Maekawa, MD, PhD¹^*

¹Department of Transfusion and Cell Therapy, Kyoto University Hospital, Kyoto, Japan
²Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan
³Avalon pharmaceuticals

1082

Differential Expression of miRNAs during the Course of Chronic Myeloid Leukemia

Katerina Machova Polakova¹^*, Tereza Lopotova¹^*, Hana Klamova²^* and Jana Moravcova¹^*

¹Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague, Czech Republic
²Inpatient Department, Institute of Hematology and Blood Transfusion, Prague, Czech Republic

1083

Chronic Myeloid Leukemia with Deletions on Der(9) Shows Mir-199b Downregulated Expression

Francesco Albano¹^*, Luisa Anelli¹^*, Antonella Zagaria¹^*, Alessandra Pannunzio¹^*, Antonella Russo Rossi¹^*, Vincenzo Liso¹^*, Mariano Rocchi²^* and Giorgina Specchia¹

¹Hematology - University of Bari, Bari, Italy
²Dept. of Genetics and Microbiology, University of Bari, Bari, Italy

1084

Lineage-Specific Regulation of miRNA-Expression by the BCR-ABL Oncogene

Michaela Scherr, PhD^*, Letizia Venturini, PhD^*, Karin Battmer^*, Arnold Ganser, MD, PhD and Matthias Eder, MD^*

Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany

1085

Bcr-Abl Promotes CML Cell Proliferation through the Suppression of PHLPP Expression

Isao Hirano¹^*, Satoki Nakamura²^*, Daisuke Yokota¹^*, Takaaki Ono¹^*, Kazuyuki Shigeno³^*, Shinya Fujisawa⁴^*, Kaori Shinjo³^* and Kazunori Ohnishi, MD, PhD¹

¹Cancer Center, Hamamatsu University School of Medicine, Hamamatsu city, Japan
²Department of Internal Medicine III, Hamamatsu university school of medicine, Hamamatsu city, Japan
³Department of Internal Medicine III, Hamamatsu University School of Medicine, Hamamatsu city, Japan
⁴Devision of Hematology, Hamamatsu Medidcal Center, Hamamatsu city, Japan

1086

Short –Term Intense Bcr-Abl Kinase Inhibition Is Adequate to Trigger Cell Death in CML Cell Lines but Not in CML-CD34+ Cells Unless They Are Growth Factor Deprived

Devendra K. Hiwase, MD, Deborah L. White, PhD^*, Verity A. Saunders^*, Junia V. Melo, MD, PhD^*, Sharad Kumar, PhD^* and Timothy P. Hughes, MD

Haematology Division, IMVS, Adelaide, Australia

1087

Xeroderma Pigmentosum Group B Binding Contributes to p210 BCR/ABL Mediated Transformation in CML

Nicole L Pannucci¹^*, Sutapa Sahay¹^*, Emily K Thomas²^*, Ru Chen¹^*, Nicholas J Megjugorac¹^*, Homer C Adams III¹^*, Pedro L Rodriguez¹^*, Ethan R Fitzpatrick¹^*, David A. Williams, MD³ and Ian P Whitehead¹^*

¹Microbiology and Molecular Genetics, New Jersey Medical School-University Hospital Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ
²Division of Experimental Hematology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Memorial Center, Cincinnati, OH
³Chief, Div. of Hematology/Oncology, Children's Hospital Boston, Leland Fikes, Boston, MA

1088

Inhibiting Alternative Non Homologus Endjoining (NHEJ) Pathways: Therapeutic Targets in Chronic Myeloid Leukemia (CML)

Annahita Sallmyr, PhD, Lisa Tobin^*, Alan E. Tomkinson^* and Feyruz V. Rassool^*

School of Medicine, Univ. of Maryland, Baltimore, MD

1089

Genome-Wide Analysis of Genetic Alterations in Chronic Myelogenous Leukemia

Charles G Mullighan, MBBS(Hons), MSc, MD¹, Ina Radtke, PhD¹^*, Jinghui Zhang, Ph.D.²^*, Letha A. Phillips, BS¹^*, Xiaoping Su, PhD¹^*, Jing Ma, PhD³^*, Zhongling Cai¹^*, Timothy P. Hughes, MBBS, PhD⁴, Deborah L White, PhD⁴^*, Andrew W. Roberts, MBBS, PhD⁵, Lynda J. Campbell, MBBS, FRCPA⁶^*, Sheila A. Shurtleff¹^* and James R. Downing, MD¹^*

¹Pathology, St. Jude Children's Research Hospital, Memphis, TN
²National Cancer Institute, Rockville, MD
³Hartwell Center, St. Jude Children's Research Hospital, Memphis, TN
⁴Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia
⁵Div. of Cancer and Haem., The Walter & Eliza Hall Inst. of Med. Rsch., Parkville, VIC, Australia
⁶Cytogenetics, St Vincent's Hospital, Melbourne, Australia

1090

Imatinib Induced Re-Activation of FoxO3 Transcription Factor in CML Is Responsible for the Induction of a Quiescent Status of CD34 Leukaemic Progenitor Cells

Daniela Cilloni, MD, PhD¹, Cristina Panuzzo, PhD²^*, Francesca Messa, PhD¹^*, Francesca Arruga, PhD³^*, Enrico Bracco, PhD¹^*, Roberto Bernardoni, PhD⁴^*, Sonia Carturan, PhD¹^*, Marisa Pautasso, MD¹^*, Emanuela Messa, MD¹^*, Alessandro Morotti, MD¹^*, Monica Pradotto, PhD¹^*, Ilaria Iacobucci⁵^*, Thea Kalebic, MD⁶^*, Giovanni Martinelli, MD⁷^* and Giuseppe Saglio, MD⁸

¹Dept. Of Clinical and Biological Sciences, University of Turin, Turin, Italy
²Department of Clinical and Biological Sciences, University of Turin, Orbassano,Turin, Italy
³Department of Clinical and Biological Science, University of Turin at Orbassano, Orbassano, Turin, Italy
⁴Seragnoli Institute of Hematology, University of Bologna, Bologna, Italy
⁵Department of Hematology and Oncological Sciences "L. e A. Seràgnoli", University of Bologna, Bologna, Italy
⁶Novartis Oncology Clinical Development NJ
⁷Department of Hematology and Oncological Sciences, University of Bologna, Bologna, Italy
⁸Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

1091

Identification of Genes Sustaining Bcr-Abl Oncogenic Signalling and CML Progression through a Genetic Tool Based on Human Bcr-Abl Transgenic Drosophila Melanogaster

Daniela Cilloni¹, Francesca Messa, PhD²^*, Roberto Bernardoni, PhD³^*, Francesca Arruga, PhD⁴^*, Monica Pradotto, PhD⁴^*, Enrico Bracco, PhD¹^*, Cristina Panuzzo, PhD²^*, Chiara Maffè, PhD⁴^*, Emanuela Messa, MD⁵^*, Ilaria Iacobucci⁶^*, Thea Kalebic, MD⁷^*, Giovanni Martinelli, MD⁸^*, Michele Baccarani, MD⁹^* and Giuseppe Saglio, MD¹^*

¹Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
²Department of Clinical and Biological Sciences, University of Turin, Orbassano,Turin, Italy
³Seragnoli Institute of Hematology, University of Bologna, Bologna, Italy
⁴Dept. Of Clinical and Biological Sciences, University of Turin, Turin, Italy
⁵Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy
⁶Department of Hematology and Oncological Sciences "L. e A. Seràgnoli", University of Bologna, Bologna, Italy
⁷Novartis Oncology Clinical Development NJ
⁸Department of Hematology and Oncological Sciences, University of Bologna, Bologna, Italy
⁹Dept. Hematology and Medical Oncology, University of Bologna, Bologna, Italy

1092

EphA3 Kinase Is Constitutively Activated in Chronic Myeloid Leukaemia during Progression to Accelerated and Blast Crisis and It Could Represent a New Molecular Target

Daniela Cilloni, MD, PhD¹, Francesca Arruga, PhD²^*, Sonia Carturan, PhD³^*, Francesca Messa, PhD³^*, Monica Pradotto, PhD⁴^*, Ilaria Defilippi, PhD³^*, Marisa Pautasso, MD¹^*, Ilaria Iacobucci, PhD⁵^*, Giovanni Martinelli, MD⁶^*, Enrico Bracco, PhD¹^*, Thea Kalebic, MD⁷^*, Martin Lackmann, PhD⁸^* and Giuseppe Saglio, MD¹

¹Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
²Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy
³Department of Clinical and Biological Sciences, University of Turin, Orbassano,Turin, Italy
⁴Dept. Of Clinical and Biological Sciences, University of Turin, Turin, Italy
⁵Department of Hematology and Oncological Sciences, Seragnoli Institute, University of Bologna, Bologna, Italy
⁶Department of Hematology and Oncological Sciences, University of Bologna, Bologna, Italy
⁷Novartis Oncology Clinical Development NJ
⁸Dept. of Biochemistry and Molecular Biology, University of Victoria, VIctoria, Australia

1093

Nck Beta Adapter Protein Coordinates Bcr-Abl/Sam68 Intermolecular Interaction

Enrico Bracco, PhD¹^*, Erika Deklic¹^*, Valentina Rosso¹^*, Stefano Mussino, PhD¹^*, Francesca Arruga, PhD¹^*, Sonia Carturan, PhD¹^*, Francesca Messa, PhD¹^*, Ilaria Defilippi, PhD¹^*, Cristina Panuzzo, PhD¹^*, Paolo Nicoli¹^*, Emanuela Messa, MD¹^*, Antonia Rotolo¹^*, Roberto Pedrola¹^*, Alessandro Morotti, MD²^*, Alessandra Balbo¹^*, Ilaria Iacobucci, PhD³^*, Giovanni Martinelli³^*, Daniela Cilloni¹^* and Giuseppe Saglio¹^*

¹Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
²Department of Clinical and Biological Sciences, University of Turin, Orbassano, Turin, Italy
³Department of Hematology and Oncological Sciences, Seragnoli Institute, University of Bologna, Bologna, Italy

1094

Evaluation of the Role of PlGF and the Therapeutic Potential of Anti-PlGF in BCR/ABL+ Leukemia

Sonja Loges, M.D., Ph.D¹^*, Thomas Schmidt, M.D.¹^*, Maria Kleppe¹^*, Kim De Keersmaecker, Ph.D.²^*, Marc Tjwa, M.D., Ph.D.¹^*, Christa Maes, Ph.D.³^*, Christiane DeWolf-Peeters, M.D., Ph.D.⁴^*, Geert Carmeliet, M.D., Ph.D.³^*, Jan Cools, Ph.D.², Jean-Marie Stassen, Ph.D.⁵^* and Peter Carmeliet, M.D., Ph.D.¹^*

¹VIB, K.U.Leuven, Vesalius Research Center, Leuven, Belgium
²VIB11, VIB, Leuven, Belgium
³Laboratory of Experimental Medicine and Endocrinology (LEGENDO), K.U. Leuven, Leuven, Belgium
⁴Department of Pathology, K.U.Leuven, Leuven, Belgium
⁵ThrombogenicsNV, Leuven, Belgium

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^*signifies non-member of ASH

631.P1.59 Chronic Myeloid Leukemia - Biology and Pathophysiology Excluding Therapy Poster I