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631.O1.8 Chronic Myeloid Leukemia - Pathophysiology and Tyrosine Kinase Inhibitors

Monday, December 8, 2008: 3:30 PM-5:30 PM
2001-2003-2014-2016 - West (Moscone Center)
Moderators:
Andreas Hochhaus and Tomasz Skorski, MD, PhD
3:30 PM
Structural Positioning of the SH2 Domain Is Critical for Bcr-Abl Kinase Activity, Signal Transduction and Oncogenic Transformation

Oliver D. Hantschel, PhD, Florian Grebien, Ines Kaupe* and Giulio Superti-Furga*

CeMM- Ctr. for Molecular Med., Vienna, Austria

3:45 PM
Distinct Gab2-Mediated Signaling Pathways Are Essential for Myeloid or Lymphoid Transformation and Leukemogenesis by BCR-ABL

M. Golam Mohi, PhD1, Wayne W. Chan, BA2*, Shaoguang Li, MD, PhD3*, Benjamin Neel, MD, PhD4* and Richard A. Van Etten, MD, PhD5*

1Dept. of Pharmacology, SUNY Upstate Medical University, Syracuse, NY
2Molecular Oncology Research Institute and Division of Hematology/Oncology,, Tufts Medical Center, Boston, MA
3University of Massachusetts Medical School, Worcester, MA
4Ontario Cancer Institute, Toronto, ON, Canada
5Molecular Oncology Research Institute and Division of Hematology/Oncology, Tufts Medical Center, Boston, MA

4:00 PM
Lymphoid Blast Crisis Transformation and Development of Drug-Resistance in Chronic Myeloid Leukemia Are Driven by Aberrant Somatic Hypermutation

Lars Klemm1*, Cihangir Duy1*, Niklas Feldhahn2*, John Groffen1*, Yong-mi Kim1*, Wolf-Karsten Hofmann, MD3*, Hassan Jumaa4*, Michael R Lieber5*, Rafael Casellas6* and Markus Muschen1

1Leukemia Research Program, Childrens Hospital Los Angeles, Los Angeles, CA
2Molecular Immunology, Rockefeller University, New York, NY
3MILE Study Group, on Behalf of European LeukemiaNet (ELN, WP13), Munich, Germany
4Molecular Immunology, Max-Planck-Institute for Immunology, Freiburg, Germany
5University of Southern California, Los Angeles, CA
6National Institutes of Health,, Genomic Integrity and Immunity, NIAMS, Bethesda,, MD

4:15 PM
Functional p53 Is Required for Effective Telomerase Inhibition in BCR-ABL-Positive CML Cells in Vitro

Ute Brassat1*, Stefan Balabanov1*, Melanie Braig1*, Daniel Bali2*, Kerstin Borgmann2* and Tim H. Brummendorf1

1Dept. of Oncology and Hematology with Sections BMT and Pneumology, Hubertus Wald-University Cancer Center, (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2Lab. of Radiobiology & Exp. Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

4:30 PM
Clonal Expansion of T/NK-Cells during Tyrosine Kinase Inhibitor Dasatinib Therapy

Satu Mustjoki, MD, PhD1, Marja Ekblom, MD, PhD2*, T. Petteri Arstila, MD, PhD3*, Ingunn Dybedal, MD, PhD4*, PK Epling-Burnette, PhD5*, Felix Garzon, MD, PhD6, Tobias Gedde-Dahl, MD, PhD4*, Sari Hernesniemi, MSc1*, Henrik Hjorth-Hansen, MD, PhD7*, Martin Hoglund, MD, PhD8, Vesa Juvonen, PhD9*, Veli Kairisto, MD, PhD9*, Panu Kovanen, MD, PhD3*, Anna Kreutzman, MSc1*, Tuisku Laurinolli3*, Jane Liesveld, MD10, Ronald Paquette, MD11, Javier Pinilla, MD, PhD5, Auvo Rauhala, MD, PhD12*, Neil Shah, MD, PhD13, Bengt Simonsson, MD, PhD8, Marjatta Sinisalo, MD, PhD14*, Juan Luis Steegmann, MD, PhD15, Leif Stenke, MD, PhD16, Jukka Vakkila, MD, PhD3* and Kimmo Porkka, MD, PhD1

1Hematology Research Unit, Department of Medicine, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
2Lund University Central Hospital, Lund, Sweden
3Departments of Immunology and Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland
4Rikshospitalet University Hospital, Oslo, Norway
5H Lee Moffitt Cancer Center and Research Institute, Tampa, FL
6Pharmaceutical Research Institute, Wallingford, CT
7Department of Hematology, St. Olavs Hospital and Department of Molecular Medicine and Cancer Research, Trondheim, Norway
8Uppsala University Hospital, Uppsala, Sweden
9TYKSLAB, Turku University Central Hospital, Turku, Finland
10Univ. of Rochester Med. Ctr., Rochester, NY
11Ronald Reagan UCLA Medical Center, Los Angeles, CA
12Vaasa Central Hospital, Vaasa, Finland
13University of California, San Francisco, San Francisco, CA
14Tampere University Hospital, Tampere, Finland
15Hospital Universitario de la Princesa, Madrid, Spain
16Karolinska University Hospital, Stockholm, Sweden

4:45 PM
Gamma Delta T Cells (GDTCs) to Eliminate Minimal Residual Disease (MRD) in Chronic Myeloid Leukemia (CML) : A Pre-Clinical Model

Gabrielle Melanie Siegers, PhD1*, Bassim Malas Al-Beirouti, MD1*, Alister Mark Mathieson, MSc.1*, Tania Cristina Felizardo, PhD2*, Simone Helke1*, Jeffrey A. Medin, PhD2 and Armand Keating, MD1

1Cell Therapy Program, Princess Margaret Hospital/Ontario Cancer Institute, Toronto, ON, Canada
2University Health Network, Ontario Cancer Institute, Toronto, ON, Canada

5:00 PM
Clonal Hematopoiesis in Philadelphia Chromosome-Negative Bone Marrow Cells of Chronic Myeloid Leukemia Patients Receiving Tyrosine Kinase Inhibitors

Ron Paquette, MD1, John Nicoll1*, Meenal Chalukya1*, Lukasz P Gondek, MD, PhD2*, Monika Jasek3*, Charles Sawyers, MD4*, Neil Shah, MD, PhD5 and Jaroslaw Maciejewski3

1University of California, Los Angeles, Los Angeles, CA
2Hematologic Oncology and Blood Disorders/Experimental Hematology and Hematopoiesis Section, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
3Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH
4Human Oncology and Pathogenesis Program, MSKCC, Howard Hughes Medical Institute, New York
5University of California, San Francisco, San Francisco, CA

5:15 PM
Switch Pocket Inhibitors of the ABL Tyrosine Kinase: Distinct Kinome Inhibition Profiles and in Vivo Efficacy in Mouse Models of CML and B-Lymphoblastic Leukemia Induced by BCR-ABL T315I

Richard A. Van Etten, MD, PhD1, Wayne W. Chan, BA1*, Virginia M. Zaleskas, MD1*, Christoph Walz, MD1*, Peter Evangelista, BA1*, Katherine Lazarides, BS1*, Monica Betancur, MS1*, Scott Wise, MS2*, Peter A. Petillo, PhD2* and Daniel L. Flynn, PhD2*

1Molecular Oncology Research Institute and Division of Hematology/Oncology, Tufts Medical Center, Boston, MA
2Deciphera Pharmaceuticals, Lawrence, KS

*signifies non-member of ASH