50th ASH Annual Meeting and Exposition (December 6 - 9, 2008): Genomic Pharmacology And Mechanisms of Drug Resistance

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

Yerba Buena Ballroom Salon 8 (San Francisco Marriott)

Moderators:

Charles Dumontet, MD, PhD and William Plunkett, PhD

7:00 AM

A Genome-Wide Approach Identifies Variations in the Aspartate Metabolism Pathway That Are Associated with Asparaginase Sensitivity

Shih-Hsiang Chen, MD¹^*, Wenjian Yang, PhD²^*, Yiping Fang, PhD³^*, Gabriele Stocco, PhD²^*, Kristine R. Crews, PharmD²^*, Ching-Hon Pui, MD⁴, William E. Evans, PharmD² and Mary V. Relling, PharmD²

¹Division of Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan
²Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN
³Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN
⁴Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN

7:15 AM

214

A Whole Genome Analysis Identifies SLCO1B1 as a Determinant of Methotrexate Pharmacokinetics and Adverse Effects

Lisa R Trevino, Ph.D.¹, Noriko Shimasaki, M.D.², Wenjian Yang, Ph.D.¹^*, John C. Panetta, Ph.D.¹^*, Cheng Cheng, Ph.D.³^*, Deqing Pei, M.S.³^*, Diana Chan, M.S.¹^*, Alex Sparreboom, Ph.D.¹^*, Kathleen M Giacomini, Ph.D.⁴^*, Ching-Hon Pui, M.D.¹^*, William E. Evans, Pharm.D.¹^* and Mary V. Relling, Pharm.D.¹^*

¹Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN
²Oncology, St Jude Children's Research Hospital, Memphis, TN
³Biostatistics, St Jude Children's Research Hospital, Memphis, TN
⁴Pharmaceutical Sciences and Pharmacogenomics, University of California, San Francisco, San Francisco, CA

7:30 AM

215

Gene Expression Profiling of Acute Myeloid Leukemia Shows Therapeutically Meaningful Patterns of Association with Ara-CTP Pharmacokinetics and Pharmacodynamics

Jatinder K. Lamba¹, Kristine Crews²^*, Stanley Pounds³^*, Xueyuan Cao³^*, Sharyn D. Baker²^*, Varsha Gandhi⁴^*, William Plunkett⁵^*, James R. Downing⁶^*, Jeffrey Rubnitz⁷ and Raul C. Ribeiro⁷

¹Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN
²Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN
³Biostatistics, St. Jude Children's Research Hospital, Memphis, TN
⁴U.T. M.D. Anderson Cancer Center, Houston, TX
⁵M.D. Anderson Cancer Center, Houston, TX
⁶St. Jude Children's Research Hospital, Memphis, TN
⁷St. Jude Children's Rsch. Hosp., Memphis, TN

7:45 AM

216

TNF-a Polymorphism Modulates the Outcome of Multiple Myeloma Patients Treated with Bortezomib

Gabriele Buda¹^*, Alessandro Martino²^*, Valentina Maggini²^*, Enrico Orciuolo¹^*, Sara Galimberti¹^*, Massimo Gentile³^*, Marino Brunori⁴^*, Fortunato Morabito⁵^*, Anna Maria Rossi²^* and Mario Petrini, MD⁶

¹Dept. of Oncology, Transplants and Advanced Technologies, University of Pisa, Pisa, Italy
²Dept. of Biology, University of Pisa, Pisa
³Unità Operativa di Ematologia, Azienda Ospedaliera dell'Annunziata, Cosenza, Cosenza, Italy
⁴Marche Multiple Myeloma Network (GEMaMM)
⁵O.U. Haematology, Azienda Ospedaliera, Cosenza, Italy
⁶Oncology, University of Pisa, Pisa, Italy

8:00 AM

217

Impaired up-Regulation of Polo-Like Kinase 2 (PLK2) during Fludarabine- and 2-Chlorodeoxyadenosine (CdA)-Induced Cell Killing in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Lymphocytes: A Potential Marker of Defective Damage Response

Emeline de Viron¹^*, Laurent Knoops²^*, Thierry Connerotte³^*, Caroline Smal¹^*, Lucienne Michaux³^*, Pascale Saussoy³^*, Françoise Bontemps¹^* and Eric Van Den Neste, MD, PhD⁴

¹Laboratory of Physiological Chemistry, de Duve Institute, Brussels, Belgium
²Hematology, Cliniques Universitaires Saint-Luc and de Duve Institute, UCL, Brussels, Belgium
³Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
⁴Hematology, Cliniques universitaires Saint-Luc, Brussels, Belgium

8:15 AM

218

Expression of the ULBP Ligands for NKG2D by B-NHL Cells Plays An Important Role in Determining Their Susceptibility to Rituximab-Induced ADCC

Atsushi Inagaki^*, Takashi Ishida^*, Hiroki Yano^*, Fumiko Mori^*, Asahi Ito^*, Masaki Ri^*, Jianmin Ding^*, Shigeru Kusumoto^*, Hirokazu Komatsu^*, Shinsuke Iida^* and Ryuzo Ueda

Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

8:30 AM

219

Compartment-Specific Bioluminescence Imaging (CS-BLI) High-Throughput Assays Provide Comparative Insights into the Impact of Osteoclasts Vs. Stromal Cells on Activity of Anti-Myeloma Therapeutics

Melissa G. Ooi^*, Douglas W. McMillin^*, Joseph M. Negri^*, Jake Delmore^*, Steffen Klippel^*, Nicholas Mitsiades^*, Paul G. Richardson^*, Kenneth C. Anderson^* and Constantine S. Mitsiades

Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA

8:45 AM

220

The Role of Mcl-1 Expression and Phosphorlyation in Resistance to Chemotherapy and Kinase Inhibitors in FLT3-ITD-Positive Acute Myeloid Leukemia (AML)

Florian H Heidel, MD¹^*, Henning Schulze-Bergkamen, MD²^*, Binje Vick²^*, Daniel B Lipka, MD³^*, Fian K Mirea³^*, Toni Urbanik²^*, Joseph T Opferman, PhD⁴^* and Thomas Fischer, MD¹^*

¹Hematology/Oncology, University Hospital Magdeburg, Magdeburg, Germany
²Hepatology/Gastroenterology, University Hospital Mainz, Mainz, Germany
³Hematology/Oncology, University Hospital Mainz, Mainz, Germany
⁴Biochemistry, St. Judes Children Research Hospital, Memphis, TN

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^*signifies non-member of ASH

604.O1.8 Genomic Pharmacology And Mechanisms of Drug Resistance