50th ASH Annual Meeting and Exposition (December 6 - 9, 2008): Pathophysiology and Translational Models

Monday, December 8, 2008: 7:00 AM-9:00 AM

2009-2011-2022-2024 - West (Moscone Center)

Moderators:

Nizar J. Bahlis, MD and John A. Lust, MD, PhD

7:00 AM

DNA Double Strand Breaks Induction by Zalypsis, a Novel Marine Compound, Results in Potent Antimyeloma Activity

Enrique M Ocio¹^*, Patricia Maiso¹^*, Xi Chen¹^*, Mercedes Garayoa¹^*, Stela Álvarez-Fernández¹^*, Laura San-Segundo¹^*, David Vilanova¹^*, Lucía López-Corral¹^*, Juan Carlos Montero¹^*, Teresa Hernández-Iglesias¹^*, Enrique de Álava¹^*, Carlos Galmarini²^*, Pablo Avilés²^*, Carmen Cuevas²^*, Atanasio Pandiella¹^* and J.F. San Miguel, MD, PhD¹

¹Centro de Investigación del Cáncer. IBMCC/CSIC, University of Salamanca, Salamanca, Spain
²Pharmamar, Madrid, Spain

7:15 AM

246

The Heparanase Inhibitor SST0001 Is a Potent Inhibitor of Myeloma Growth In Vivo

Yang Yang¹, Joseph P. Ritchie¹^*, Telisha Swain¹^*, Annamaria Naggi²^*, Giangiacomo Torri²^*, Benito Casu²^*, Claudio Pisano³^*, Paolo Carminati⁴^*, Israel Vlodavsky⁵^* and Ralph D. Sanderson¹^*

¹Department of Pathology, Center for Metabolic Bone Disease and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL
²G.Ronzoni Institute for Chemical and Biochemical Research, Milan, Italy
³sigma-tau Industrie Farmaceutiche Riunite S.p.A., Pomezia, Italy
⁴sigma-tau Research Switzerland SA, Milan, Italy
⁵Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel

7:30 AM

247

Proteasome Stress Causes Apoptotic Sensitivity of Multiple Myeloma Cells to Proteasome Inhibition

Giada Bianchi¹^*, Laura Oliva²^*, Paolo Cascio³^*, Niccolo' Pengo²^*, Andrea Orsi²^*, Francesca Fontana²^*, Elena Pasqualetto²^*, Alexandre Mezghrani⁴^*, Fulvia Cerruti³^*, Valeria Calbi⁵^*, Giovanni Palladini⁶^*, Nicola Giuliani⁷, Dharminder Chauhan¹^*, Kenneth C. Anderson¹^*, Roberto Sitia²^* and Simone Cenci²^*

¹Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
²Department of Biology and Technology, DiBiT, San Raffaele Scientific Institute, Milan, Italy
³Department of Veterinary Morphophysiology, University of Turin, Turin, Italy
⁴Institut of Genetique Humaine, CNRS, Montpellier, France
⁵Hematology and BMT Unit, San Raffaele Scientific Institute, Milan, Italy
⁶Center for Amyloidosis, Fondazione IRCCS Policlinico San Matteo and Department of Biochemistry, University of Pavia, Italy
⁷Unit of Hematology and BMT, University of Parma, Parma, Italy

7:45 AM

248

Inhibition of Aurora-Kinases for Tailored Risk-Adapted Treatment of Multiple Myeloma

Dirk Hose¹, Thierry Rème²^*, Tobias Meißner¹^*, Jérôme Moreaux²^*, Anja Seckinger¹^*, Joe Lewis³^*, Vladimir Benes³^*, Axel Benner⁴^*, Michael Hundemer¹^*, Thomas Hielscher⁴^*, John D. Shaughnessy Jr., PhD⁵, Bart Barlogie⁵^*, Kai Neben¹^*, Alwin Krämer¹^*, Jens Hillengass¹^*, Uta Bertsch¹^*, Anna Jauch⁶^*, John De Vos²^*, Jean François Rossi²^*, Thomas Möhler¹^*, Jonathon Blake³^*, Jürgen Zimmermann³^*, Bernard Klein²^* and Hartmut Goldschmidt¹^*

¹Medizinische Klinik V, Univeristätsklinikum Heidelberg, Heidelberg, Germany
²INSERM U847, Montpellier, France
³European Molecular Biology Laboratory, Heidelberg, Germany
⁴Abteilung für Biostatistik, Deutsches Krebsforschungszentrum, Heidelberg, Germany
⁵Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR
⁶Univeristätsklinikum Heidelberg, Institut für Humangenetik, Heidelberg, Germany

8:00 AM

249

Preclinical Studies Using Polyethylenimine (PEI) Nanoparticles Complexed with Eukaryotic Translation Initiation Factor 5A (eIF5A) siRNA and eIF5A^K50R Plasmid DNA Demonstrates Significant Anti-Myeloma Activity in Vitro and in Vivo

John A. Lust, MD, PhD¹, John E. Thompson, PhD²^*, Catherine A. Taylor, PhD²^*, Bin Ye²^*, Zhongda Liu²^*, Zhong Sun²^*, Richard S. Dondero, PhD³^*, Laurie L. Moon-Tasson¹^*, Michael P. Kline, PhD¹^* and Kathleen A. Donovan, PhD¹^*

¹Hematology, Mayo Clinic, Rochester, MN
²Biology, University of Waterloo, Waterloo, ON, Canada
³Senesco Technologies, New Brunswick, NJ

8:15 AM

250

Integration of DNA Copy Number and Gene Expression Alterations Reveal Novel Insights into the Molecular Pathogenesis and Prognosis of Multiple Myeloma

Yiming Zhou, PhD¹^*, Bart Barlogie, MD, PhD¹, Damir Herman, PhD¹^*, Owen Stephens, PhD¹^*, Erming Tian, PhD¹^*, David Williams, PhD¹^*, Marie-astrid Cartron, PhD¹^*, Frits van Rhee, MD, PhD¹^*, Mauricio Pineda-Roman, MD, PhD¹^*, Yazan Alsayed, MD, PhD¹^*, Elias Anaissie, MD, PhD¹, Jeffrey Sawyer, Ph.D.²^* and John D. Shaughnessy Jr., PhD¹

¹Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR
²Pathology, University of Arkansas for Medical Sciences, Little Rock, AR

8:30 AM

251

AT7519, a Novel Small Molecule Multi-Cyclin Dependent Kinase Inhibitor, Induces Apoptosis in Multiple Myeloma VIA GSK3β

Loredana Santo, MD¹^*, Sonia Vallet, M.D.²^*, Teru Hideshima, M.D., Ph.D.¹, Diana Cirstea, MD¹^*, Samantha Pozzi, MD¹^*, Nileshwari Vaghela²^*, Hiroshi Ikeda, MD, PhD¹, Yutaka Okawa, MD¹^*, Gullu Gorgun, PhD¹, Giulia Perrone, MD¹^*, Elisabetta Calabrese, MD¹^*, Matthew S Squires³^*, Marco Ladetto, MD⁴, Nikhil C. Munshi, MD¹^*, Mario Boccadoro⁴^*, Kenneth C. Anderson, MD¹^* and Noopur Raje, MD¹^*

¹Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
²Hematology-Oncology, Massachusetts General Hospital, Boston, MA
³Astex Therapeutics Ltd., Cambrigde, United Kingdom
⁴Division of Hematology, University of Turin, Turin, Italy

8:45 AM

252

Preclinical Evaluation of CRx-501, a Potent Selective A2A Agonist as a Novel Drug Candidate for the Treatment of Multiple Myeloma

Richard J Rickles, Ph.D.¹^*, Laura Pierce¹^*, Thomas Giordano¹^*, William Avery²^*, Melissa Farwell²^*, David Crowe²^*, Winnie F. Tam, Ph.D.¹^*, Mei Chen, Ph.D.¹^*, Vikram Kansra, PhD²^*, Douglas W. McMillin, BSc, PhD³^*, Kenneth C Anderson, MD³, Constantine Mitsiades, M.D., Ph.D.³ and Margaret S. Lee, PhD²^*

¹CombinatoRx, Incorporated, Cambridge, MA
²CombinatoRx, Inc., Cambridge, MA
³Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA

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^*signifies non-member of ASH

652.O1.8 Pathophysiology and Translational Models