57th ASH Annual Meeting and Exposition (December 5-8, 2015): 605. Molecular Pharmacology, Drug Resistance – Lymphoid and Other Diseases: Diverse Mechanisms of Drug Resistance

Molecular Pharmacology, Drug Resistance – Lymphoid and Other Diseases Oral and Poster Abstracts
Oral

W312, Level 3 (Orange County Convention Center)

Moderators:

Jun J Yang, PhD, St. Jude Children's Research Hospital and Monique L. Den Boer, PhD, Erasmus MC - Sophia Children's Hospital

Disclosures:

No relevant conflicts of interest to declare.

7:00 AM

445

T-Cell Acute Lymphoblastic Leukemia Patients with Mutations in IL7Ra or Downstream RAS-MEK or PI3K-AKT Can be Collectively Targeted By Combination of RAS and AKT Inhibitors

Kirsten Canté-Barrett, PhD¹, Jill AP Spijkers-Hagelstein²^*, Jessica GCAM Buijs-Gladdines¹^*, Wilco K Smits¹^*, Rogier C Buijsman, PhD²^*, Guido JR Zaman, PhD²^*, Rob Pieters, MD, PhD^1,3 and Jules PP Meijerink, PhD¹

¹Department of Pediatric Oncology/Hematology, Erasmus MC - Sophia Children's Hospital, Rotterdam, Netherlands
²Netherlands Translational Research Center B.V., Oss, Netherlands
³Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands

7:15 AM

446

NT5C2 As a Major Contributor to Thiopurine Resistance at ALL Relapse Via Multiple Mechanisms

Takaya Moriyama, MD^1,2, Julia Meyer, PhD^3,4^*, Shuguang Liu, PhD^1,5^*, Xujie Zhao¹^*, Zhaohong Ying, MD¹^*, William L. Carroll, MD^3,4,6 and Jun J Yang, PhD⁷

¹Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN
²Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan
³New York University Cancer Institute, New York University Langone Medical Center, New York, NY
⁴Department of Pathology, New York University Langone Medical Center, New York, NY
⁵Hematology Oncology Center, Beijing Children’s Hospital, Beijing, China
⁶Department of Pediatrics, New York University Langone Medical Center, New York, NY
⁷Dep. Pharm. Sci., Hematologic Malignancies Program, St. Jude Children's Research Hospital, Memphis, TN

7:30 AM

447

Emergence of Fc-Gamma-Riib-Dominance Contributes to Resistance to Therapeutic Antibodies in Patients with Chronic Lymphocytic Leukaemia

Melinda Burgess^1,2^*, Sally Mapp, MBBS, PhD, FRACP, FRCPA^3,4^*, Roberta Mazzieri, PhD^1,2^*, Jonathan Ellis, BSc, MSc, PhD^1,2^*, Catherine Cheung⁴^*, Lynne Chambers³^*, Stephen Mattarollo, BSc, PhD^1,2^*, Peter Mollee, MBBS, MMedSc, FRACP, FRCPA^2,4,5, Devinder Gill, MB FRCPath FRACP FRCPA^2,6 and Nicholas Saunders, BSc, PhD^1,2^*

¹University of Queensland Diamantina Institute, Brisbane, Australia
²Translational Research Institute, Brisbane, Australia
³Haematology Dept, Princess Alexandra Hospital, Brisbane, Australia
⁴School of Medicine, University of Queensland, Brisbane, Australia
⁵Princess Alexandra Hospital, Brisbane, Australia
⁶Haematology, Princess Alexandra Hospital, Brisbane, Australia

7:45 AM

448

Ligands That Mimic the Tissue Microenvironment of Replicating Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) Protect Ex Vivo Patient Cell Samples from the Cytotoxicity of Combined Treatment with Ibrutinib and Venetoclax (ABT-199)

Kallesh D. Jayappa, Ph.D.¹^*, Craig A. Portell, MD^2,3, Vicki Gordon, B.S.¹^*, Michael E. Williams, MD^2,4, Emanuel F. Petricoin, Ph.D.⁵^*, Timothy P. Bender, PhD^1,6^* and Michael J. Weber, PhD^1,2^*

¹Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA
²Cancer Center, University of Virginia, Charlottesville, VA
³Division of Hematology/Oncology, University of Virginia School of Medicine, Charlottesville, VA
⁴Division of Hematology/Oncology, University of Virginia Health System, Charlottesville, VA
⁵Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA
⁶Beirne B. Carter Center for Immunology Research, University of Virginia School of Medicine, Charlottesville, VA

8:00 AM

449

Diverse Mechanisms of Vemurafenib Resistance in BRAF-Mutant Hairy Cell Leukemia

Jae H Park, MD¹, Stephen S. Chung, MD¹, Benjamin Durham, MD, PhD²^*, Young Rock Chung, MS³^*, Sasinya Scott, MPH²^*, Bartlomiej Getta, MBBS,²^*, Eunhee Kim, PhD²^*, Alan Saven, MD⁴, Richard M. Stone, MD⁵, Kanti R Rai, MD⁶, Michael R. Grever, MD⁷, Jessica K. Altman, MD⁸, Neal Rosen, MD, PhD⁹^*, Ross L. Levine, MD², Michael Berger, PhD¹⁰^*, Martin S Tallman, MD¹ and Omar Abdel-Wahab²

¹Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
²Memorial Sloan Kettering Cancer Center, New York, NY
³Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY
⁴Scripps Health, La Jolla, CA
⁵Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
⁶North Shore Long Island Jewish Health Systems, New Hyde Park, NY
⁷Division of Hematology and Oncology, The Ohio State University, Columbus, OH
⁸Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
⁹Pharmacology, Memorial Sloan Kettering Cancer Center, New York
¹⁰Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

8:15 AM

450

Crispr Sgrnas Genome-Wide Screen Identifies the Proteasome Regulatory Subunit PSMC6 As a Bortezomib Resistance Gene in Human Multiple Myeloma Cells

Chang-Xin Shi, Ph.D.¹^*, Klaus M Kortum, M.D.¹^*, Yuan Xiao Zhu, PhD¹^*, Patrick Jedlowski¹^*, Esteban Braggio, PhD¹, Laura Ann Bruins²^*, Patrick G. Votruba, M.S.³^*, Moulun Luo, Ph.D.⁴^*, Robert A. Stewart⁵^*, Jonathan M. Ahmann⁵^* and A. Keith Stewart²

¹Division of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ
²Mayo Clinic, Scottsdale, AZ
³Department of Infomation Techonology, Mayo Clinic, Scottsdale
⁴Mayo/ASU Center for Metabolic and Vascular Biology, Arizona State University, Scottsdale
⁵Division of Hematoloty/Oncology, Mayo Clinic, Scottsdale

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^*signifies non-member of ASH

605.O1.6 605. Molecular Pharmacology, Drug Resistance – Lymphoid and Other Diseases: Diverse Mechanisms of Drug Resistance