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604.O1.8 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
A Whole Genome Analysis Identifies SLCO1B1 as a Determinant of Methotrexate Pharmacokinetics and Adverse EffectsClinically Relevant Abstract

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
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
TNF-a Polymorphism Modulates the Outcome of Multiple Myeloma Patients Treated with BortezomibClinically Relevant Abstract

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
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
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
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
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

*signifies non-member of ASH