57th ASH Annual Meeting and Exposition (December 5-8, 2015): 641. CLL: Biology and Pathophysiology, excluding Therapy: Signaling and Targeted Drug Therapies for CLL

CLL: Biology and Pathophysiology, excluding Therapy Oral and Poster Abstracts
Oral

W304ABCD, Level 3 (Orange County Convention Center)

Moderators:

John Gribben, MD, DSc, Barts Cancer Institute, Queen Mary University of London and Tait D. Shanafelt, M.D., Mayo Clinic

Disclosures:

Gribben: Pharmacyclics: Honoraria ; Roche/Genentech: Honoraria ; Gilead: Honoraria ; Janssen: Honoraria ; Celgene: Consultancy , Honoraria . Shanafelt: Polyphenon E International: Research Funding ; Celgene: Research Funding ; Pharmacyclics: Research Funding ; Cephalon: Research Funding ; Hospira: Research Funding ; Jannsen: Research Funding ; Glaxo-Smith-Kline: Research Funding ; Genentech: Research Funding .

7:00 AM

487

Ibrutinib Responsive Micro-RNAs and Upregulation of Tumor Suppressor Targets in Chronic Lymphocytic Leukemia

Layla M Saleh, M.D.^1,2^*, Weixin Wang, Ph.D.¹^*, Sarah E. M. Herman, PhD³^*, Mohammed Farooqui, DO³, Clare Sun, MD³, Emily Barber, B.S.¹^*, Meghan Corrigan-Cummins, B.S.¹^*, Nakhle Saba, MD³^*, Hasan Awad, M.D., Ph.D.²^*, Adrian Wiestner, MD, PhD³ and Katherine R. Calvo, MD, PhD¹

¹Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
²Clinical Pathology, Mansoura University Hospital, Mansoura, Egypt
³Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

7:15 AM

488

Subversion of Pkca and Pkcbii Upregulation Play an Essential Role in Chronic Lymphocytic Leukaemia Development, Inducing Constitutive B Cell Receptor-Mediated Signals

Anuradha Tarafdar, PhD^*, Ashfia Fatima Khan, M Pharm^*, Emilio Cosimo, Bsc, PhD^*, Hothri A. Moka, BSc hons^*, Karen Dunn, BSc hons^* and Alison M. Michie, PhD, BSc^*

Paul O'Gorman Leukaemia Research Centre, University of Glasgow, Glasgow, United Kingdom

7:30 AM

489

Inhibition of SYK More Effectively Overcomes MCL-1 Mediated ABT-199 Resistance of BCR-Stimulated CLL Cells Than Inhibition of BTK or PI3Kdelta

Kamil Bojarczuk, PhD^1,2^*, Binu K Sasi, PhD¹^*, Stefania Gobessi, PhD¹, Idanna Innocenti, MD³^*, Luca Laurenti, MD³^* and Dimitar G Efremov, MD, PhD¹

¹Molecular Hematology, ICGEB, Rome, Italy
²Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland
³Institute of Hematology, Catholic University of the Sacred Heart, Rome, Italy

7:45 AM

490

Ibrutinib Therapy Increases BCL-2 Dependence and Enhances Sensitivity to Venetoclax in CLL

Jing Deng¹^*, Elif Isik¹^*, Stacey M. Fernandes¹^*, Jennifer R. Brown, MD, PhD², Anthony Letai, MD, PhD¹ and Matthew S. Davids, MD³

¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
²Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA
³Dana-Farber Cancer Institute, Boston, MA

8:00 AM

491

MYD88 L265P Mutations Influence Clinical Outcome and Identify a Pathway for Targeted Inhibition in Chronic Lymphocytic Leukemia

Bethany Tesar, MS^1,2^*, Reina Improgo, PhD^1,2, Josephine L. Klitgaard, MSc, PhD^2,3^*, Reuma Magori-Cohen^4,5^*, Lijian Yu^1,2^*, Divya Chaudhary⁶^*, Wenyan Miao⁶^*, Stacey M. Fernandes³^*, Kevin Hoang¹^*, William F Westlin⁶, Haesook T. Kim, PhD⁷^* and Jennifer R. Brown, MD, PhD^2,8

¹Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA
²Department of Medicine, Harvard Medical School, Boston, MA
³Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
⁴Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA
⁵Department of Biostatistics, Harvard School of Public Health, Boston, MA
⁶Nimbus Therapeutics, Inc, Cambridge, MA
⁷Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA
⁸Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

8:15 AM

492

The Gain of the Short Arm of Chromosome 2 (2p+) Induces XPO1 Overexpression and Drug Resistance in Chronic Lymphocytic Leukemia

Adrien Cosson¹^*, Elise Chapiro, MD, PhD^1,2^*, Jérome Lambert, PhD³^*, Hong-Anh Cung¹^*, Caroline Algrin, MD^1,4^*, Frédérik Damm, MD, PhD⁵^*, Clémentine Gabillaud²^*, Frederic Davi^1,2^*, Hélène Merle-Béral, MD, PhD^1,2^*, Sylvain Choquet, MD⁴^*, Madalina Uzunov, MD⁶^*, Véronique Morel, MD²^*, Veronique Leblond, MD⁴, Karim Maloum, MD, PhD⁷, Stéphane Leprêtre, MD⁸^*, Pierre Feugier, MD, PhD⁹^*, Claude Lesty¹⁰^*, Julie Lejeune³^*, Laurent Sutton, MD¹¹^*, Santos A. Susin, PhD¹^* and Florence Nguyen-Khac, MD, PhD^2,12^*

¹Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers - INSERM UMRS1138, Paris, France
²Groupe Hospitalier Pitié-Salpêtrière, Paris, France
³Hôpital Saint Louis, Assistance Publique - Hôpitaux de Paris, Paris, France
⁴Department of Clinical Hematology, Pitie-Salpetriere Hospital and Pierre et Marie Curie University, Paris, France
⁵Genetics of Tumors, Institut Gustave Roussy - INSERM U1170, Villejuif, France
⁶Hematology Department, Pitie-Salpetriere Hospital, Paris, France
⁷Department of Biological Hematology, Pitie-Salpetriere Hospital and Pierre et Marie Curie University, Paris, France
⁸Service d'Hématologie, Hôpital Becquerel, Rouen, France
⁹CHU et INSERM 954, Nancy Université, Vandoeuvre Les Nancy, France
¹⁰Groupe Hospitalier Pitie-Salpetriere, Paris, France
¹¹Hematology Department, Argenteuil Hospital, Argenteuil, France
¹²Department of Biological Hematology, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers - INSERM UMRS1138, Paris, France

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^*signifies non-member of ASH

641.O3.6 641. CLL: Biology and Pathophysiology, excluding Therapy: Signaling and Targeted Drug Therapies for CLL