65th ASH Annual Meeting & Exposition: 641. Chronic Lymphocytic Leukemias: Basic and Translational: Molecular Determinants of CLL and Richter Transformation

Symposia: Chronic Lymphocytic Leukemias: Basic and Translational Oral and Poster Abstracts
Oral

Research, Fundamental Science, Lymphoid Leukemias, Biological therapies, Antibody Therapy, apoptosis, artificial intelligence (AI), adult, Translational Research, CLL, Lymphomas, non-Hodgkin lymphoma, assays, elderly, B Cell lymphoma, Combination therapy, bioinformatics, Checkpoint Inhibitor, drug development, hematopoiesis, Diseases, indolent lymphoma, immune mechanism, Therapies, Immunotherapy, therapy sequence, immunology, Lymphoid Malignancies, metabolism, computational biology, Monoclonal Antibody Therapy, Biological Processes, emerging technologies, molecular biology, Technology and Procedures, Study Population, Human, pathogenesis, imaging, Animal model, molecular testing, Pathology

Grand Hall B (Manchester Grand Hyatt San Diego)

Moderators:

Ingo Ringshausen, MD, University of Cambridge and Erin M Parry, MD, PhD, Brigham & Women's Hospital/Massachusetts General Hospital

Disclosures:

Ringshausen: AstraZeneca: Research Funding; Varsity Pharma: Research Funding.

9:30 AM

Glycerolipid Metabolism Via the MGA-MYC-NME1-PGP Axis As a Key Regulator of Oxidative Phosphorylation in Richter's Transformation

Prajish Iyer, PhD¹^*, Brian Jiang²^*, Girish Venkataraman, MD, MBBS³, Joo Y Song, MD^4,5^*, Tanya Siddiqi, MD^6,7, Steven T. Rosen, MD^8,9, Alexey Danilov, MD^10,11 and Lili Wang, MD/PhD¹²

¹Department of Systems Biology, Beckman Research Institute, City of Hope National Comprehensive Cancer, Monrovia, CA
²Department of Systems Biology, Beckman Research Institute, City of Hope National Comprehensive Cancer, Monrovia
³Department of Pathology, University of Chicago, Chicago, IL
⁴Department of Pathology, City of Hope National Medical Center, Duarte, CA
⁵Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA
⁶Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
⁷Toni Stephenson Lymphoma Center, Beckman Research Institute, Duarte
⁸City of Hope Comprehensive Cancer Center, Toni Stephenson Lymphoma Center, Beckman Research Institute, Duarte, CA
⁹Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
¹⁰Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
¹¹Toni Stephenson Lymphoma Center, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA
¹²Department of Systems Biology, City of Hope Comprehensive Cancer Center, Duarte, CA

9:45 AM

CXCR4 Loss Reduces the Local Growth of Richter Syndrome Murine and Patient-Derived Xenograft Models and Impairs BCR and VLA-4 Activation

Claudio Martines, PhD¹^*, Supriya Chakraborty, PhD¹^*, Antonella Zucchetto, PhD²^*, Erika Tissino, PhD³^*, Vincenzo Guastafierro, MD¹^*, Marija Vujovikj, MS⁴^*, Tiziana Vaisitti, PhD⁵, Silvia Deaglio, MD, PhD⁶, Luca Laurenti, MD⁷^*, Aleksandar J Dimovski, MD, PhD⁴^*, Valter Gattei, MD⁸ and Dimitar G Efremov, MD, PhD¹

¹Molecular Hematology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
²Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
³Clinical and Experimental Onco-Hematology Unit, Centro Di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
⁴RCGEB, Macedonian Academy of Sciences and Arts, Skopje, MKD
⁵Dept. of Medical Sciences, Hugef Human Genetics Foundation, Torino, To, Italy
⁶Dept. of Medical Sciences, University of Turin, Turin, Italy
⁷Division of Hematology, Fondazione Universitaria Policlinico A Gemelli di Roma, Rome, Italy
⁸Centro Di Riferimento Oncologico, Aviano, Italy

10:00 AM

CD49d Shapes B Cell Receptor Responsiveness and Tissue Distribution in an Aggressive Chronic Lymphocytic Leukemia Murine Model

Laura Polcik^1,2^*, Danielle-Justine Danner³^*, Riccardo Bomben⁴^*, Tamara Bittolo⁴^*, Lixia Li, PhD³^*, Driti Ashok^2,3^*, Sandra Kissel³^*, Natalie Koehler, PhD^3,5^*, Andrea Härzschel, PhD³^*, Geoffroy Andrieux, PhD^6,7^*, Melanie Boerries, MD, PhD^8,9^*, Sophia Engel^2,3^*, Theresa Haslauer, PhD¹⁰^*, Jan Hoepner, PhD¹⁰^*, Nadja Zaborsky, PhD¹⁰^*, Richard Greil, MD¹⁰, Cornelius Miething, MD³^*, Khalid Shoumariyeh, MD¹¹^*, Jesus Duque Afonso, MD¹², Justus Duyster, MD¹³^*, Antonella Zucchetto, PhD¹⁴^*, Valter Gattei, MD¹⁵ and Tanja Nicole Hartmann, PhD¹⁶

¹Department of Internal Medicine I, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, German, Freiburg, Germany
²Faculty of Biology, University of Freiburg, Freiburg, Germany
³Department of Internal Medicine I, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
⁴CRO Aviano National Cancer Institute,Clinical and Experimental Onco-Hematology Unit, Aviano, Italy
⁵CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany
⁶Institute of Medical Bioinformatics and Systems Medicine, Medical Center – University of Freiburg, Faculty of Medicine, Freiburg, Germany
⁷German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
⁸Institute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
⁹German Cancer Consortium (DKTK), Partner site Freiburg; and German Cancer Research Center (DKFZ), Heidelberg, Germany
¹⁰Paracelsus Medical University, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute - Laboratory for Immunological and Molecular Cancer Research (SCRI-LIMCR), Salzburg, Austria
¹¹Department of Medicine I, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
¹²Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany
¹³Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, University of Freiburg, Freiburg, Germany
¹⁴Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
¹⁵Centro Di Riferimento Oncologico, Aviano, Italy
¹⁶Department of Internal Medicine I, Medical Center University Freiburg, Freiburg, Germany

10:15 AM

The Integrin Adaptor Kindlin-3 Is a Gatekeeper for Germinal Center Responses and the Development of Chronic Lymphocytic Leukemia

Lixia Li, PhD¹^*, Andrea Härzschel, PhD¹^*, Peter Krenn, PhD²^*, Danielle-Justine Danner¹^*, Laura Polcik^3,4^*, Adrián Fernández-Rego⁵^*, Jennifer Schönbeck¹^*, Melissa Riedle⁶^*, Sandra Kissel¹^*, Cornelius Miething, MD¹^*, Justus Duyster, MD¹^*, Natalie Koehler, PhD^1,7^*, Susanna Fagerholm, PhD⁸^*, Yolanda Carrasco, PhD⁵^*, Palash Maity, PhD⁶^* and Tanja Nicole Hartmann, PhD⁹

¹Department of Internal Medicine I, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
²Department of Biosciences, Paris-Lodron University Salzburg, Salzburg, AUT
³Department of Internal Medicine I, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, German, Freiburg, Germany
⁴Faculty of Biology, University of Freiburg, Freiburg, Germany
⁵Department of Immunology & Oncology, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain
⁶Institute of Experimental Cancer Research, Medical Faculty, University Ulm, Ulm, Germany
⁷CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany
⁸Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland
⁹Department of Internal Medicine I, Medical Center University Freiburg, Freiburg, Germany

10:30 AM

Loss of DDX3X Function Promotes CLL Progression By Facilitating NOTCH1 mRNA Translation

Yi Miao, MD^*, Jing Zhang^*, Huayuan Zhu^* and Jianyong Li, MD

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China

10:45 AM

Pre-Clinical Study on the Dual BCL2/BCL-XL Inhibitor AZD0466 for the Treatment of Chronic Lymphocytic Leukemia

Billy Jebaraj, PhD¹^*, Rashmi Priyadharshini Dheenadayalan, PhD²^*, Annika Müller, PhD³^*, Jialei Qi³^*, Eugen Tausch, MD⁴^*, Christof Schneider, MD⁵^*, Daniela Steinbrecher, PhD³^*, Daniel Mertens, PhD³^*, Felix Seyfried⁶^*, Lüder Hinrich Meyer, Prof. Dr.⁶^*, André Lechel, PhD⁷^*, Barbara F. Eichhorst, MD⁸, Courtney L Andersen, PhD⁹^*, Giulia Fabbri, MD, PhD¹⁰^* and Stephan Stilgenbauer, MD¹

¹Department of Internal Medicine III, Division of CLL, University Hospital Ulm, Ulm, Germany
²University of Ulm, Ulm, Germany
³University Hospital Ulm, Ulm, Germany
⁴Department of Internal Medicine III, Division of CLL, Ulm University, Ulm, Germany
⁵Division of CLL, Department of Internal Medicine III, University of Ulm, Ulm, Germany
⁶Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany
⁷Ulm University Hospital, Ulm, Germany
⁸University of Cologne, Cologne, Germany
⁹AstraZeneca Early Oncology R&D TDE, Waltham, MA
¹⁰Oncology R&D AstraZeneca, Waltham, MA

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^*signifies non-member of ASH

641.O1.6 641. Chronic Lymphocytic Leukemias: Basic and Translational: Molecular Determinants of CLL and Richter Transformation